15. neuroplasticity


Published on

Published in: Health & Medicine
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

15. neuroplasticity

  1. 1. Neuroplasticity Tutorial By: Dr Madhumita Sen
  2. 2. Introduction• What is brain plasticity?• Does it mean that our brains are made of plastic?• Of course not!• Plasticity, or neuroplasticity, is the lifelong ability of the brain to reorganize neural pathways based on new experiences.• As we learn, we acquire new knowledge and skills through instruction or experience
  3. 3. • Definition: Neural plasticity, which is also known as neuroplasticity, brain plasticity, cortical plasticity, is the changing of the structure, function, and organization of neurons in response to new experiences.• Neural plasticity specifically refers to strengthening or weakening nerve connections or adding new nerve cells based on outside experiences.
  4. 4. HowPathsarecreated
  5. 5. • In some cases, patients with brain damage have healed naturally because healthy nerves took on the tasks of damaged or destroyed nerves, allowing for at least some level of functionality.• There are a variety of mechanisms by which neural plasticity can occur; axonal sprouting and synaptic pruning are among the most common of these mechanisms.
  6. 6. Axonal Sprouting• In axonal sprouting, healthy axons sprout new nerve endings that connect to other pathways in the nervous system.• This can be used to strengthen existing connections or to repair damaged parts of the nervous system by repairing damaged neural pathways and restoring them to full functionality.
  7. 7. Synaptic Pruning• Following birth, the brain of a newborn is flooded with information from the baby’s sense organs.• This sensory information must somehow make it back to the brain where it can be processed.• To do so, nerve cells must make connections with one another, transmitting the impulses to the brain.
  8. 8. • Over the first few years of life, the brain grows rapidly.• As each neuron matures, it sends out multiple branches (axons, which send information out, and dendrites, which take in information), increasing the number of synaptic contacts and laying the specific connections from house to house, or in the case of the brain, from neuron to neuron.
  9. 9. • At birth, each neuron in the cerebral cortex has approximately 2,500 synapses.• By the time an infant is two or three years old, the number of synapses is approximately 15,000 synapses per neuron (Gopnick, et al., 1999).• This amount is about twice that of the average adult brain.• As we age, old connections are deleted through a process called synaptic pruning.
  10. 10. • Synaptic pruning eliminates weaker synaptic contacts while stronger connections are kept and strengthened.• Experience determines which connections will be strengthened and which will be pruned; connections that have been activated most frequently are preserved.• It is plasticity that enables the process of developing and pruning connections, allowing the brain to adapt itself to its environment.
  11. 11. • Because of axonal sprouting and synaptic pruning that lend to neural plasticity, damage to the brain or other aspects of the nervous system is not always permanent.• This process is part of what makes humans so able to adapt to a broad range of circumstances; the very physiology of the brain changes in response to a given set of conditions. Contrary to common ideas as expressed in this diagram, brain functions are not confined to certain fixed locations.
  12. 12. Network of our Brain• The communication network in our brain is a multi-trillion maze of connections capable of performing 20 million-billion calculations per second.• How does this network operate?• There are three major players:• Neurons, which power the message,• Neurotransmitters, which create the message and• Receptors, which receive the message.
  13. 13. • A single one of our neurons can produce almost a tenth of a volt, and the total electrical activity in our brain is easily measurable with an electroencephalogram (EEG).• The impulse then travels at a speed of up to 150MPH away from the cell body through its antennae, the axon.
  14. 14. Neurotransmitters – Chemical Transmission• Dopamine is the neurotransmitter needed for healthy assertiveness and sexual arousal, proper immune and autonomic nervous system function.• Dopamine is important for motivation and a sense of readiness to meet lifes challenges.• Age-related cognitive decline is associated with dopamine changes in the brain.• People whose hands tremble from Parkinsons disease have a diminished ability to synthesize dopamine, which is crucial to fine muscle coordination.• Attention deficits are also connected to dopamine.
  15. 15. • It is one of the most vulnerable key neurotransmitters in the brain.• Dopamine levels are depleted by stress or poor sleep.• Alcohol, caffeine, and sugar all seem to diminish dopamine activity in the brain.• Its also easily oxidized, therefore we should eat plenty of fruits and vegetables whose antioxidants help protect dopamine-using neurons from free radical damage.
  16. 16. • Norepinephrine, also called noradrenalin, is the primary excitatory neurotransmitter needed for motivation, alertness, and concentration.• A hormone, it travels in the bloodstream to arouse brain activity with its adrenalin-like effects.• Our brain requires norepinephrine to form new memories and to transfer them to long- term storage.
  17. 17. • Both nor-epinephrine and dopamine are manufactured from the amino acids tyrosine or phenylalanine in the presence of adequate oxygen, vitamins B3(Niacin), B6(Pyridoxine), and C, folic acid, iron, and copper.• Food sources of tyrosine include almonds, avocados, bananas, dairy products, lima beans, pumpkin seeds, and sesame seeds.
  18. 18. • Serotonin is a calming neurotransmitter important to the maintenance of good mood.• It promotes contentment and is responsible for normal sleep.• In addition to the central nervous system, serotonin is also found in the walls of the intestine (the enteric nervous system) and in platelet cells that promote blood clotting.
  19. 19. • Low serotonin levels produce insomnia and depression, aggressive behaviour, increased sensitivity to pain, and is associated with obsessive-compulsive behaviour and eating disorders.• Serotonin is synthesized from tryptophan in the presence of adequate vitamins B1, B3, B6, and folic acid.• The best food sources of tryptophan include bananas, brown rice, cottage cheese, meat, turkey, spinach, peanuts, and sesame seeds.
  20. 20. • Glutamate and GABA :• These two are the most common neurotransmitters in the brain.• Glutamate acts on several different types of receptors, and have effects that are excitatory and modulatory.• Excessive glutamate can cause neural apoptosis.• GABA also acts on several different types of receptors that are inhibitory.• GABA is synthesised from glutamate.• Glutamate rich foods are milk, eggs, meat, fish, cheese, soya and walnuts.
  21. 21. • Acetylcholine is the primary chemical carrier of thought and memory.• This excitatory neurotransmitter is essential for both the storage and recall of memory, and partly responsible for concentration and focus.• It also plays a significant role in muscular coordination.• A deficit in acetylcholine is directly related to memory decline and reduced cognitive capacity.
  22. 22. • Its primary building block is choline, which belongs to the B family of vitamins and is a fat-like substance thats necessary to metabolize fats.• It is found in lecithin as phosphatidyl choline.• Foods high in lecithin include egg yolks, wheat germ, soybeans, organ meats, and whole wheat products.• Vitamin C and B5 (Pantothenic acid) are needed for the brain to synthesize acetylcholine, in the presence of choline acetyl-transferase, a key brain enzyme.• Acetylcholine levels tend to decline with age, in part because of a decreased ability to synthesize this enzyme.
  23. 23. Receptors-Open the Doors• A receptor is essentially a geomagnetic lock designed to accept only the right key – the neurotransmitter whose molecular shape and polarity are a precise fit.• The typical receptor is a large molecule. The exposed section, the lily pad, floats on the surface of the cell membrane, while the roots extend deep into the cell.
  24. 24. • There are as many kinds of receptors as there are neurotransmitters.• Receptors are Protein molecules.• Although each receptor is supposed to recognize and accept only a particular neurotransmitter molecule, certain medicines and plant compounds are also able to mate with some receptors.
  25. 25. • Receptors Decline with Age• The neurotransmitter serotonin interacts with at least 15 different receptors in the body.• After age 20, one of serotonins most common receptors starts to decline in the human brain.• Receptors for the neurotransmitter dopamine also decline with age.
  26. 26. Neurons• Neurons are the core components of the nervous system, which includes the brain, spinal cord, and peripheral ganglia.• Neurons do not undergo cell division.• In most cases, neurons are generated by special types of stem cells.• Astrocytes, a type of glial cell, have been observed to turn into neurons by virtue of the stem cell characteristic pluripotency.• This is called “recruitment.”
  27. 27. • The key to neural function is the synaptic signalling process, which is partly electrical and partly chemical.• The electrical aspect depends on properties of the neurons membrane.• Every neuron is surrounded by a plasma membrane, a bilayer of lipid molecules with many types of protein structures embedded in it.• To build brain cells we need fatty acids.• A lipid layer also coats the axon (Myelin), acting as insulation for electrical impulses.• One of the most common fatty acids in myelin is oleic acid, which is also the most abundant fatty acid in human milk.
  28. 28. • From ALA and LA, the 2 essential FAs, our brain can make (docosahexaenoic acid) DHA and (arachidonic acid) AA, the longer chained fatty acids that are incorporated in its cell membranes.• The brains ability to assemble these fatty acids can be compromised by stress, infections, alcohol, excess sugar, and vitamin or mineral deficiencies – factors common today.
  29. 29. • Also, the oxidative damage that comes with age causes a decline in membrane DHA concentrations, and with it, cognitive impairment.• Essential Fatty Acids have been shown to actually boost intelligence and an imbalance of fatty acids may be linked to hyperactivity, depression, brain allergies, and schizophrenia.
  30. 30. Blood Vessels• Any discussion of the brain must include the vast network of blood vessels that serve it.• There are 400 miles of capillaries in the human brain having a surface area of approximately 100 square feet.• And, the health of these vessel walls is paramount to proper brain function. Hence avoidance of trans fats.
  31. 31. • Not only is the bloodstream a river of life constantly delivering oxygen, glucose, and nutrients to the brain – and removing toxins – it also cools the brain.• One of the bloodstreams important functions is to keep brain cells from overheating.
  32. 32. History• During most of the 20th century, the general consensus among neuroscientists was that brain structure is relatively immutable after a critical period during early childhood.• This belief has been challenged by findings revealing that many aspects of the brain remain plastic even into adulthood
  33. 33. • In 1793, Italian anatomist Michele Vicenzo Malacarne described experiments in which he paired animals, trained one of the pair extensively for years, and then dissected both.• He discovered that the cerebellums of the trained animals were substantially larger.• But, these findings were eventually forgotten.• The first person to use the term neural plasticity appears to have been the Polish neuroscientist Jerzy Konorski.
  34. 34. • A tragic stroke that left his father paralyzed inspired Prof. Paul Bach-y-Rita, an American neuroscientist, to study brain rehabilitation.• His brother, a physician, worked tirelessly to develop therapeutic measures which were so successful that the father recovered complete functionality by age 68 and was able to live a normal, active life which even included mountain climbing.• "His father’s story was first hand evidence that a ‘late recovery’ could occur even with a massive lesion in an elderly person.
  35. 35. Phantom limbs• The experience of Phantom limbs is a phenomenon in which a person continues to feel pain or sensation within a part of their body which has been amputated.• This is strangely common, occurring in 60- 80% of amputees.
  36. 36. • An explanation for this refers to the concept of neuroplasticity, as the cortical maps of the removed limbs are believed to have become engaged with the area around them in the post-central gyrus (sensory cortex).• This results in activity within the surrounding area of the cortex being misinterpreted by the area of the cortex formerly responsible for the amputated limb.
  37. 37. • In the early 1990s V.S. Ramachandran theorized that phantom limbs were the result of cortical remapping.• However, cortical remapping occurs only in patients who have phantom pain.• Research showed that phantom limb pain (rather than referred sensations) was the perceptual correlate of cortical reorganization.• This phenomenon is sometimes referred to as maladaptive plasticity.
  38. 38. A diagrammatic explanation of the mirror box.• The patient places the good limb into one side of the box (in this case the right hand) and the amputated limb into the other side.• Due to the mirror, the patient sees a reflection of the good hand where the missing limb would be.• The patient thus receives artificial visual feedback that the "resurrected" limb is now moving when they move the good hand.
  39. 39. • In 2009 Lorimer Moseley and Peter Brugger carried out a remarkable experiment in which they encouraged arm amputee subjects to use visual imagery to contort their phantom limbs into impossible configurations.• Four of the seven subjects succeeded (as recorded on fMRI scans).• This experiment suggests that nerves can still be used to execute impossible movements in the absence of feedback from the body: “the brain truly does change itself."
  40. 40. Thinking About Thinking• As scientists probe the limits of neuroplasticity, they are finding that mind sculpting can occur even without input from the outside world.• The brain can change as a result of the thoughts we think.• This has important implications for health: thought can affect the very stuff of the brain, altering neuronal connections in a way that can treat mental illness or, perhaps, lead to a greater capacity for empathy and compassion.• It may even dial up the supposedly immovable happiness set point!
  41. 41. • In a series of experiments, Jeffrey Schwartz and colleagues at the University of California, Los Angeles, found that cognitive behavior therapy (CBT) can quiet activity in the circuit that underlies obsessive- compulsive disorder (OCD), just as drugs do.• Schwartz had become intrigued with the therapeutic potential of mindfulness meditation, the Buddhist practice of observing ones inner experiences as if they were happening to someone else.
  42. 42. • When OCD patients were plagued by an obsessive thought, Schwartz instructed them to think, "My brain is generating another obsessive thought thrown up by a faulty circuit."• After 10 weeks of mindfulness-based therapy, 12 out of 18 patients improved significantly.• Before-and-after brain scans showed that activity in the orbital frontal cortex, the core of the OCD circuit, had fallen dramatically and in exactly the way that drugs against OCD affect the brain.• Schwartz called it "self-directed neuroplasticity," concluding that "the mind can change the brain."
  43. 43. Plasticity of Learning and Memory• Learning, as defined by Tortora and Grabowski (1996), is the ability to acquire new knowledge or skills through instruction or experience.• Initially, newly learned data are "stored" in short-term memory, which is a temporary ability to recall a few pieces of information• After a period of time, information may be moved into a more permanent type of memory, long-term memory, which is the result of anatomical or biochemical changes that occur in the brain.
  44. 44. • The human brain now faces a challenge never before encountered in its thousands of generations of development. Modern food processing techniques have actually altered a basic building block of the brain.• Trans fatty acids found in foods disrupt communication in our brain. By modifying natural fats, we have altered the basic building blocks of the human brain – weakening the brain’s architecture.
  45. 45. Factors that control neurogenesis:• Experiences:• Enriched environment increases promotion of cell survival• Exercise increases rate of cell division• Learning tasks increase synapse formation• Stress reduces neurochemicals• Growth factors increase: Epidermal growth factor favours differentiation into glial cells, whereas fibroblasts growth factors promote neuronal production.
  46. 46. • Serotonin increases axonal sprouting and synapse formation.• Estrogen, testosterone increases brain neurotropic hormones.• Glucocorticoids (stress) reduce synapse formation and axonal sprouting. Chronic stress can reduce the number of dendritic spines• Damage: Epileptic seizures and Stroke cause permanent nerve tissue damage but also stimulate an increase in nerve regeneration.• Genetics
  47. 47. Injury-induced Plasticity: Brain Repair• During brain repair following injury, plastic changes are geared towards maximizing function in spite of the damaged brain (animal studies).• Although this phenomenon has not been widely studied in humans, data indicate that changes occur in human brains following injury.
  48. 48. • An important aspect of neuroplasticity involves the monitoring of neurotransmitter activities.• Specific receptors help neurons sense the environment and turn the genes which cause production of neurotransmitters and their receptors on or off.• For example, if an individual has just experienced a stressful situation, the brain senses the rise in stress level and may turn off or turn down the genes that make neurotransmitter receptors.
  49. 49. • Acute and chronic stress can have quite different effects on learning:• Acute stress can potentiate learning ( Shors, 2001),• Chronic stress leads to deficits in hippocampus- dependent memory reminiscent of those seen in major depression.
  50. 50. Neuroplasticity and Depression• Evidence has accumulated that structural changes in the limbic system may be related to major depression.• Duman suggests that major depression and other affective disorders could result in loss of neuroplasticity.
  51. 51. • Scientists at the University of Toronto had 14 depressed adults undergo CBT, which teaches patients to view their own thoughts differently-- to see a failed date, for instance, not as proof that "I will never be loved" but as a minor thing that didnt work out.• Thirteen other patients received paroxetine (the generic form of the antidepressant Paxil).• All experienced comparable improvement after treatment.• Then the scientists scanned the patients brains.
  52. 52. • Surprise !• Depressed brains responded differently to the two kinds of treatment--and in a very interesting way.• CBT muted overactivity in the frontal cortex, the seat of reasoning, logic and higher thought.• Paroxetine, by contrast, raised activity there.• CBT raised activity in the hippocampus of the limbic system, the brains emotion center.• Paroxetine lowered activity there.
  53. 53. Happiness and Meditation• Could thinking about thoughts in a new way affect not only such pathological brain states as OCD and depression but also normal activity?• To find out, neuroscientist Richard Davidson of the University of Wisconsin at Madison turned to Buddhist monks, the Olympic athletes of mental training.• Some monks have spent more than 10,000 hours of their lives in meditation
  54. 54. • During the generation of pure compassion, brain regions that keep track of what is self and what is other became quieter, fMRI showed, as if the subjects opened their minds and hearts to others.• Connections from the frontal regions, so active during compassion meditation, to the brains emotional regions seemed to become stronger with more years of meditation practice.
  55. 55. • But perhaps the most striking difference was in an area in the left prefrontal cortex--the site of activity that marks happiness.• While the monks were generating feelings of compassion, activity in the left prefrontal swamped activity in the right prefrontal (associated with negative moods) to a degree never seen from purely mental activity.• For the monks as well as the patients with depression or OCD, the conscious act of thinking about their thoughts in a particular way rearranged the brain.
  56. 56. How the Brain is Mapped• Positron Emission Tomography (PET) allows scientists to determine the metabolic rates of the brain by measuring oxygen and blood sugar (glucose) utilization.• Areas of the brain that are active use more oxygen and glucose than areas that are not active.
  57. 57. • Functional MRI (fMRI) also allows us to determine which parts of the brain are active.• fMRI measures blood flow. Magnets in the fMRI scanner exploit the natural magnetic properties of blood and water in the body, and create a color- coded image on a computer screen.• The fMRI image informs researchers which areas of the brain have the highest (more activity) and lowest (low activity) blood flows.
  58. 58. • The prefrontal cortex enables us to regulate emotions, and more specifically, helps us inhibit inappropriate or incapacitating emotions.• If our left prefrontal cortex is less active, then negative emotions (such as depressed mood) may be expressed more frequently and more intensely.• An active Left PC indicates a happy mood.
  59. 59. “Brainswitching”The use of simple repetitive mind exercises can switch the neural activity from the emotional part of the brain (the subcortex – limbic system), where sadness originates, to the thinking part of the brain (the neocortex) which does not have the capacity for depression.
  60. 60. • Heres an example of an exercise.• If you wake up depressed, instead of thinking "Im so depressed," think some neutral or nonsense thought over and over, repetitively, like "green frog, green frog" or "yes, yes, yes, yes," or sing a nursery rhyme to yourself like "Row, row, row, your boat."• Scream it in your mind if you have to.• Concentrate on the phrase you have chosen.• Refuse to think the thought "I am depressed."
  61. 61. • This switch in neural brain activity from the subcortex to the neocortex happens naturally, sooner or later, even in the worst cases of depression.• This is the reason depression is cyclical.• But brainswitching accomplishes the switch as an act of will and a lot more quickly than waiting for nature to take its course.• Depression is like living in a room of pain.• With brainswitching you can learn how to leave the room.
  62. 62. FRS factor• The Feelings Receptor Station in the neocortex is where signals from the emotional part of the brain (the subcortex) must travel upwards and be acknowledged in the thinking part of the brain (the neocortex) before a human being is able to feel any pain or emotion.• The FRS factor is why a player can break a bone during a football game and not feel any pain until the game is over.
  63. 63. • His neocortical concentration on the game has jammed the acknowledgment in the neocortex that pain is being produced in the subcortes.• The limitation of the human attention span is the scientific basis for mind modulation.• The mind can only concentrate on one thought at a time and you can think any thought you want.
  64. 64. • More specifically, when two targets T1 and T2 are embedded in a rapid stream of events, and presented in close temporal proximity, the second target is often not seen.• When many resources are devoted to T1 processing, too few may be available for subsequent T2 processing (the magician – rabbit experiment)• This is the basis of mindfulness meditation and MBSR.
  65. 65. Psychoneuroimmunology• Psychoneuroimmunology is a specialized field of research that studies the interactions between the brain, psychology, and the immune system.• This field primarily centres on our bodys reaction to stress.
  66. 66. • In humans, chronic stress seems to influence the serotonin, norepinephrine, and dopamine neurotransmitter systems, particularly in individuals who are socially isolated and/or have poor coping skills.• Stress also causes a decline in the rate of formation of new neurons (neurogenesis) in the part of the brain known as the hippocampus.• Autopsy evidence suggests that depressed people who experienced chronic stress and then went on to commit suicide showed reduced neurogenesis in the hippocampus
  67. 67. CAM in Neuromodulation• St. Johns Wort has been used for thousands of years, and is currently one of the top selling herbs for depression.• There are many active chemical constituents in St. Johns Wort.• These chemicals, called hypericin, pseudohypericin, and hyperforin, have all been investigated for their anti- depressant properties.
  68. 68. • Exercising as little as three hours a week can have a profound effect on the symptoms of depression.• Researchers are puzzled about the exact reason for the benefits, but studies conducted with animals suggest that exercise increases serotonin, dopamine and norepinephrine levels.• Exercise also releases endorphins, chemicals naturally produced in the body, which reduce the experience of pain and enhance neuroplasticity, thus improving mood, learning capacity and memory.
  69. 69. • Omega-3 Fatty Acids (oils), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found primarily in fish (such as mackerel, lake trout, herring, sardines, albacore tuna, and salmon) and some plants.• There is strong evidence from epidemiological (population) studies that cultures which eat large amounts of fish containing these oils have a low incidence of depression, Alzheimer’s and stress disorders.
  70. 70. • SAMe (pronounced "Sammy") stands for S- adenosyl-L-methionine. SAMe is a compound produced by the liver and used throughout the body in a chemical process called methylation.• Because there are no foods that have high SAMe levels, our bodies must make this substance.• Our liver usually creates SAMe from the amino acid methionine, which is found in many foods, with the help of vitamin B12 and folate.• The brain use of SAMe is in the creation of the neurotransmitters dopamine, serotonin and norepinephrine.
  71. 71. • 5-hydoxytryptophan (5-HTP) is a compound made from the amino acid (protein) tryptophan and is primarily found in the brain.• 5-HTP is one of the basic building blocks for serotonin.• Serotonin itself can be manufactured in the laboratory, but when taken as a supplement, it cannot reach the brain .• Multiple research studies support the use of 5- HTP as a natural way to increase brain serotonin levels.• Tryptophan rich foods are milk, bananas, spinach and turkey.
  72. 72. • B-vitamins, especially B1 (thiamin), B6 (pyridoxine), B9 (folic acid), and B12 (cobalamin) have all been examined for their contribution to neural plasticity.• These B-vitamins play many important roles in the body and are necessary for the manufacture of GABA, serotonin, dopamine, and other neurotransmitters responsible for regulating mood.
  73. 73. • Acupuncture balances yin and yang, keeps the normal flow of energy unblocked, and restores health to the body and mind.• A Western interpretation of acupuncture is that the treatment stimulates the central nervous system, releasing chemicals into the muscles, spinal cord, and brain, promoting the bodys natural healing abilities.• Acupuncture may also alter brain chemistry by changing the release of neurotransmitters and hormones that positively impact mood.
  74. 74. Meditation• Meditation was conceptualized as a family of complex emotional and attentional regulatory strategies developed for various ends, including the cultivation of well-being and emotional balance.• There are two common styles of meditation, i.e.,1. Focused attention (FA) meditation and2. Open monitoring (OM) meditation.
  75. 75. • FA meditation entails voluntarily focusing attention on a chosen object in a sustained fashion.• OM meditation involves non-reactively monitoring the content of experience from moment to moment, primarily as a means to recognize the nature of emotional and cognitive patterns.
  76. 76. • OM meditation initially involves the use of FA training to calm the mind and reduce distractions, but as FA advances, the cultivation of the monitoring skill per se becomes the main focus of practice.• The aim is to reach a state in which no explicit focus on a specific object is retained; instead, one remains only in the monitoring state, attentive moment by moment to anything that occurs in experience.
  77. 77. The Take-away• Our brains have the lifelong ability to adapt and build.• Its true! No matter how old we get, our brains are always finding new and better ways to reorganize neural pathways (information highways, if you will) and even build brand new ones.
  78. 78. • These neural "information highways" form the basis of our cognitive skills.• Cognitive skills not only make up IQ, they also determine how efficiently were able to process information in every area of our lives.• No matter how old we get, our mental abilities (and even IQ!) are never "set in stone."• Because the brain is always adapting and building, our ability to think, remember and learn is never static— it can always be upgraded and improved!
  79. 79. Q?Thank you