quiz 3
Two fairly consistent brain abnormalities in depressed individuals is hyperactivity in the amygdala
been detected across imaging studies of depressed individuals. Also, reduction in activity in prefrontal cortical structures that normally inhibit the amygdala. Also been observed in some of these imaging studies, reduced activity in prefrontal cortical structures that normally serve to inhibit the amygdala and regulate emotion. Example, dorsolateral prefrontal cortex, anterior cingulate cortex, prefrontal cortex normally serves to inhibit the amygdala, inhibitory projections. If you have a reduction in your prefrontal cortical activity, taking the breaks off of the amygdala. Depression appears to be this disruptive connectivity between prefrontal cortical structures that are involved in cognitive control and execute control. Limbic structures like amygdala involved in emotional responses.
Stress and hippocampal damage
evidence in humans in elevated cortisol levels, chronic stress are associated with reductions in the volume of the hippocampus, or the reduction in the size of the hippocampus. Disorders in humans that is characterized by excessive cortisol release is Cushing's syndrome, typically caused by some type of tumor in the hypothalamus, some type of tumor in the prituary gland which actually physically disrupts the function of the HPA axis. Result, hypersecretion of cortisol in Cushing's disease. Shown in people, severity of their hippocampus lose is directly related to the amount of cortisol in the blood stream. More excessive that cortisol release, greater the reduction in the hippocampal volume. Imaging studies, looked at combat veterans with PTSD, reduction in the size of the hippocampus. Extent of the reduction, in the size of hippocampus is associated with the duration of combat exposure, longer these individuals were exposed to combat stress, smaller the size of hippocampus.
Human beings have the same genetic defect the mice do that can be efficiently treated with leptin.
Girl with genetic leptin deficiency at age 5 and then age 9 on the right after treatment. Helped return weight to a normal range. Leptin treatment-effective in treating obese humans who have this genetic leptin deficiency. It is rare. Turns out, most cases of human obesity, obese individuals have elevated levels of leptin rather then leptin deficiency, more attopist tissue and fat tissue produces leptin. Most cases as human obesity, leptin injections wont do good, already have elevated levels of leptin. Question, most obese have enough leptin, why doesn't that leptin work to regulate body fat in a normal range. Primary hypothesis, some cases, problem isnt with leptin levels, problem is leptin sensitivity. Leptin receptors in the hypothalamus of some obese individuals may be less sensitive to leptin. Even though they have enough leptin in their body, maybe a problem rather with leptin resistance, leptin insensitivity rather than leptin level of cells. Hypothesis currently being investigated.
Studies that actually measured patterns of brain activity when subjects are engaged in learning a particular task during the day.
Later monitored, brain activity is monitored in those same subjects during sleep. Studies have been done on rodents, studies have found the pattern of activity that was present during the learning itself is reactivated during sleep, some of the same brain areas are active during sleep which subjects one of the functions of sleep is to consolidate what we learn during the day, strengthen memories for new information.
Summary of adaptive effects of the acute stress response and the damaging effects of chronic stress.
Stress responses are good and bad. Depends on the circumstances under which their expressed. Depends on how long those stress responses last. System was designed to all us to be able effectively respond to some type of acute threat, but then to return to homestatis after the stress is over.
Again, one of the reasons that the hippocampus is so susceptible is because it contains a really high concentration of glucocorticoids receptors
Under normal conditions that serves an adaptive function because it inhibits the HPA axis when the stress is over, but when you have prolonged activation of those receptors like cortisol, it is going to weaken those cells. Causes the cell death. High number of glucocorticoids receptors in the hippocampus is actually a good thing, negative feedback system is very sensitive. Bad is when you have chronic activation of those receptors by cortisol. Cortisol is chronically bound to those receptors, that is what produces the damage. High concentration of glucocorticoids is good, cortisol is constantly bound to those receptors, causes damage. Kills the neurons.
Chronic stress and the cardiovascular system
another domain where prolonged stress has been shown to have especially negative outcomes is cardiovascular health, system. Acutely, activation of the sympathetic nervous system in response to stress, increase hear rate, blood pressure, adaptive on the short term basis. But when that sympathetic activation is chronic, that can result in high blood pressure, heart disease, increase risk for heart attacks. Also damage to the blood vessels. Damage to those endothelial cells that make up the wall of the blood vessels. Effects, mediated in a couple different ways, when those levels of EPI and NE are circulating bloodstream, chronically high, that can produce direct damage to the heart muscle itself. When its been chronically stimulated by that catecholamines. EPI and NE receptors that are located on the heart muscle itself, when those receptors are chronically activated, that can produce direct damage to the heart muscle. Indirect damage to the heart, damage that results from a reduced blood supply to the heart. In the vessels that supply blood to the heart become blocked, that's how a heart attack happens. When you have chronically elevated levels of stress hormones, particularly EPI in the bloodstream, cause damage or scarring of the endothelial cells that lie in the blood vessels. When you get scarring of those endothelial cell walls, that allows blood platelets to accumulate ifn those areas, blood platelets will accumulate in those areas of damage. Plaque starts to develop and that will start to accolade the blood vessel. That can reduce or block the blood supply to the heart. This is an example askemic damage, refers to damage that is caused by a reduction of blood supply. Eskepia is when you have a blocked blood supply to a structure. Foremore, direct damage to the heart by EPI and NE, classified as non eskemic damage. Chronic stress produces both non eskemis and eskemic damage to the heart. A lot of these negative cardiovascular chronic stress, mediated by these levels of circulating stress hormones for being too high for too long. Produce direct damage to the heart or damage to the blood vessels that supply the heart.
depression
associated with reduction in hippocampal volume, some cases. Extent in the decrease in hippocampal damage is related to the severity of the depression, related to the number and the duration of untreated depressive episodes. Relationship between elevated cortisol levels and hippocampus damage in all of these disorders.de
Stress response, one principle component of the bodies response to stress is going to be activation of the sympathetic nervous system
When its activated, result in a release of NE from the sympathetic fibers on to the all of the effector organs in the body. Produces increase in hear rate, increase oxygen uptake by the lungs, increase in glucose release from the liver. All of these things that prepare the body to effienctly respond to a threat. In addition to those neural effects that are produced by this sympathetic neurons innervating each of the organs, also hormonal effects of sympathetic activation. Activation of the sympathetic system, also result in the release of epinephrine and NE from the adrenal glands, adrenal glands sit right on top of the kidneys. When we experience a stressor, adrenal glands will dump epinephine or AKA adrenaline into blood stream, dump NE in the blood stream and those hormones basically amplify the effects of sympathetic activation. Epinephrine and NE travel through the bloodstream and act on many of these same target organs to amplify the response. For example, circulating epinephrine and NE, release by the adrenal glands, act on heart, to further increase heart rate, act on some of these organs to amplify the sympathetic response. Large part of the bodies sympathetic stress response, also mediated by adrenaline and NE that is released from adrenal glands. Neural responses and also hormonal responses.
Negative feedback control of HPA axis
activation of the HPA axis by stress, negative feedback control, cortisol act back on the brain to reduce HPA activity, helps return the system to normal. After the stressor is over, don't want to have high levels of cortisol circulating in the blood stream. This is how the system is supposed to work. Want to respond to the stressor, then when stress is over, shut the system off. Evidence that this negative feedback system, dysfunctional in certain stress related disorders.
We tend to thing about the stress response as bad or negative
actually this stress response evolved as an adaptive mechanism to effectually to situations involving in acute threats, designed to go offline when the stress is over. The body is able to return to homestatis. This system not designed to respond to prolonged stress. Really common in our culture, when we are constantly stressed about something, chronic stress that produces damaging effects on body.
Diagram that summarizes major effects and sympathetic and parasympathetic
all of these organs which we don't have voluntary control, organs are innervated by two sets of fibers. Sympathetic fibers and parasympathetic, produce opposing effects on those organs. Sympathetic fibers that synapse directly to those organs, shown in green, sympathetic fibers, release NE as there neurotransmitter. Those parasympathetic fibers that synapse directly onto those organs release ACH as there neurotransmitter. Example, sympathetic neurons that innervate the heart, release NE, bind to beta receptors on the heart that will produce increase heart rate. Parasympethic neurons that innervate the heart, release ACH, bind to muscarinic receptors on the heart which will produce a decrease in heart rate. All of these organs, receive direct innervation from sympathetic neurogenetic and also parasympathetic, cholinergic fibers, control the functioning of those organs in opposite directions. Neurons that directly innervate the organs, neurons directly synapse onto the organs, called postganglionic neurons, their cell bodies lie in cell clusters or ganglia that are outside the central nervous system. Postganglionic fibers directly innervate those organs. Postganglionic neurons innervated by another set of neurons called preganglionic neurons which originate in brain stem and also in the spinal cord. This is how the autonomic nervous system is organized, those effector organs are directly innervated by both neurogenic and cholinergic fibers. Those postganglionic fibers are innervated by neurons coming from brain stem and spinal cord.
Same circuit that circuit between prefrontal cortex and amygdala
also effected in the anxiety disorders as well. Some researchers believed that depression nd anxiety, manifestation in the same disorder. A lot of overlap in the brain mechanism that underline depression and underline anxiety
depression
brain areas affected, reduction in hippocampal volume, brain changes that has been observed in depressed individuals. Not all, but many. Consistent finding. Decrease hippocampal volume, believed to be related to elevated levels of the glucorritoids, elevated levels of CRH and cortisol that are floating around in the blood stream. Cortisol chronically binds to those hippocampal glucose receptors, produces degeneration of the hippocampal neurons. American journal psychiatry-location of hippocampus, example of reduced hippocampal volume in depression relative to healthy controls. Reduction in hippocampal volume, primary brain changes have been observed in depression.
Neural systems underlying slow-wave and REM sleep
brain areas involved in different types of sleep. Forebrain-important in generating slow wave sleep, if you isolate the forebrain from lower brain areas, do a transection that isolated forebrain to lower, forebrain brain shows EEG pattern of constant slow wave sleep, stimulate forebrain in intact animal, induce slow wave sleep. By contrast, pons, lower brain, hindbrain, involves generating REM sleep, if your stimulate pons, induce REM SLEEP, lesion the pons that abolished rem sleep, abolishes muscular paralysis that accompanies REM sleep.
Sleep Stages and Characteristics
brain mechanism and Characterists of sleep. Another homeostatic system in the body that is necessary for normal and stable functioning. Spend about 1/3rd of our lives in sleep, 8 hours in 24 hour day but some get less than that. Sleep, primary activities from time standpoint. Not known for sure about the specific functions, essential, cant function without sleep on a long term basis. Discovered in past 50 years, happening in brain when we sleep even if we don't understand the functional significance of the events yet.
Parasympathetic
branch active when we are in a calm, relaxed state. Opposite to those in sympathetic system. Activation produces Decrease in heart rate, blood pressure, stimulates reproductive function and digestive organs. Mediates activities that will restore the bodies energy rather than mobilizing it.
Specific nucleus in the hypothalamus
called arcuate nucleus which monitors levels of several different hormones that are released from the body. Monitor hormones that are released from gut, fat tissues. Those hormones basically inform the hypothalamus about the energy state of the body. Whether we have enough energy or not. Hypothalamus can generate a appropriate response, either decrease or increase our food intake. This hormonal communication from the body to the brain, major mechanism that regulates appetite.
Changes in sleep patterns with age
changes in REM sleep and total amount of sleep that occurs with age, occurs as function as age. Plot , number of hours spent awake and in REM and NON rem sleep from infancy to old age. Rem and non rem sleep-constitute the total amount of daily sleep. Obvious from graph-total amount of sleep time decreases as a function of age. Infants spend close to 16 hours a day asleep , about 2/3thirs of the day, young adults, spend about 8 hours total sleep time, average, drops off further in elderly people, 6 hours per night. While there is a slight decline in NON REM sleep in age, difference is more striking in rem sleep, declines fairly with age. Infants spend much longer proportion in rem sleep than adults do. Infants spend 50% total sleep time in REM sleep, adults is primarily non rem. Hypothesized-functional significant of that larger amount of time that infants spend in rem sleep, brain development. brain activity that occurs during rem may facilitate the formation of synaptic connections, facilitate what wiring of brain that occurs early in development, stimulatory role in brain development. Based on observations-hypothesis, don't have definite evidence. Sleep is difficult to study because people are Unconcious.
Stress response and what psychological happens when we experience a stressful stimuli, chronic stress
cosistive factor in many disease states including neuropsychoactivity diseases like depression for example. Strong link between stress and depression. Brain changes observed in depression and how influenced by chronic stress. Damaging effects on brain and cardiovascular, immune system. Resilience factors research, area starting to become prominent in literature, focus not on just understanding mechanism of disease but understanding mechanism to resilience to stress.
stress
defined in different ways, broadest sense of the term stress considered any circumstance that upsets our homestatis, hemostatic balance. Aversive or threatening event that has the potential to harm us, or disrupt our well being in some way. Body evolved specific psychological mechanisms to respond to threatening stimuli. In the short-term, those are adaptive responses. Allow us to deal with an immediate threat in the environment, prolonged stress, mechanism are chronically activated, damaging effects on body and brain. Not a system that was designed to be on all the time.
CNS effects of chronic stress and depression
depression, stress and depression often go hand to hand, very high concurrence of anxiety in many depressed individuals. Tend to be comorbid disorders, anxiety and depression often occur together. One characteristic that has been associated with some cases of depression is hyperactivity of the HPA axis. Proportion of depressed patients, not all of them, certain proportion of depressed patients, blood cortisol levels and CRH levels tend to be elevated compared to healthy individuals. Depressed individuals release more stress hormones. Evidence, HPA hyperactivity in a certain proportion of depressed patients due to a faulty negative feedback system. Negative feedback system which normally inhibits HPA activity is not working properly. One test that been used to measure the functioning of that negative feedback system is the dexamethasone suppression test, synthetic glucocoridate, very similar to cortisol. Synthetic version of cortisol. If you inject this synthetic gluccortoid, inject dexamethasone into a normal healthy individual, what happens it is the blood cortisol levels will drop. That dexamethasone activates that negative feedback system, bind to glucoodtrod receptors, basically tricks the brain into thinking the blood cortisol levels are high. Activates that negative feedback system, HPA activity is inhibited. If you inject, suppresses cortisol levels, indicates that the negative feedback system is working properly, doing what its supposed to do. Many depressed individuals fail this test, if you inject dexamethasone into a depressed patient or at least this occurs in some depressed patients, there is some hederanavy there, if you inject into certain proportion in depressed patient, blood cortisol levels do not increase like they should. Suggests that normal feedback system, negative feedback system not working right, not functioning correctly. Appears to be problem with negative feedback system with some depressed individuals which is resulting in this chronically elevated levels of stress hormones.
REM Rebound
deprived of REM SLEEP, body will try to recover that rem sleeps in subsequent nights, following rem sleep deprivation, rem rebound effect. Greater proportion of time will be spent in REM sleep. Experiments in sleep labs-non deprived state, people typical adult, 20% of their total sleep time in REM sleep. But if you deprive a person of REM over several nights, waking them up every time they go through a REM episode. On subsequent nights, leaves them alone again, get this REM rebound effect, greater than normal amount of time they spend in REM sleep, enter REM sleep more quickly than normal after going to sleep. The body attempts recover REM sleep if its been deprived.
going on in brain during sleep
electrical activity during sleep- EEG recording, electroencephalogram. Involved in placing electrodes in different areas in scalp which measure the electrical activity of cells in those areas of electrodes. EEG measures overall activity of the cortex, measures activity in large population of cells. Using these EEG recording, known the brain passes through different stages of sleep, characterized by specific patterns of electrical activity. Electrical activity in brain when person is awake, someone is alert, awake, their EEG patterns show fast, very low amplitude waves, brain waves are occurring in high frequency. Fast waves indidictve of activated cortex, high level of brain activity. First enter sleep, first fall asleep, enter stage 1 sleep, also sometimes called light sleep. During stage 1 sleep, frequency of brain waves is slower, not as fast at the waking state but brain activity is still fairly high. Patten continues into stage 2 sleep, electrical events that you don't see in stage 1. brain activity starts to slow down even more, enter slow wave sleep, which comprises stages 3 and 4. during these later stages, EEG starts to show these very low frequency, high amplitude waves called DELTA waves. Delta waves, deep stages of sleep. Start to appear in stage 3 and predominate in stage 4. very slow waves, really high amplitude. High amplitude waves on EEG, caused because cells on cortex are starting to fire together in sercretiy, causes high amplitude waves, cells firing at the same time. Brain activity, high secrinaized when deep stages of sleep.
Stress and hippocampal damage
evidence that chronic stress that have direct damaging effects of the brain, produce neuronal damage, or neuronal degeneration. Chronic stress kills neurons. One of the structures that's particularly susceptible to stress induced brain damage is the hippocampus. Studies that have been done in rodents, if you inject animal daily with stress hormones, if you inject then with stress hormone over a period of several weeks, inject them with choronisontrone, rat version of cortisol. Alternatively, expose them to some type of chronic stressor over several weeks, their own body is releasing elevated levels of chorosoltrine. Dendrites of their hippocampal, start to atrophy, start to atrophy and degenerate. Stress is continued, eventually those hippocampal neurons will die. Prolonged exposure of the hippocampus to glucocorticoids, stress hormone, kills neurons.
Stress resilience
factors that have been to shown to contribute to resilience to stress, ability to adapt sucessfully to stress, some type of trauma. Area of research focused on resilience and what factors distunish indiviiausl that are resilent to stress vs individuals that are not resilient to stress.
Factors- not under our control
genetics, genetic differences between all of us as individuals that do effect our limbic reactivity to negative events. Genetic differences that effect are CRH system. Effect how much cortisol we release to the same stimulus, genetic variation is some of these HPA axis related genes for CRH , for glucocorido receptors, etc. genetic variation in genes that regulate that minoamine system, regulate serotonin and NE levels which are heavily involved in mood. Genetic differences between us in some of these system that can change our threshold in responding to the same stressful stimulus.
Also that Evidence that sleep deprivation can impairs the bodies ability to utilize
glucose and insulin appropriately which can lead to type 2 diabetes and obesity. Sleep deprivation can induce a pre diabetic state which will increase risk for type 2 diabetes and obesity. Even relatively mild sleep deprivation has also been shown to alter levels of the appetite regulating hormones, increase in ghrelin levels with sleep deprivation which promotes hunger, suppression of leptin levels in sleep deprivation and leptin is normally a satiety signal. Together, effect in increasing appetite and increasing food intake.
EEG pattern during rem sleep
high level of brain activity. EEG pattern during rem, looks like a awake brain, brain in stage 1 sleep or light sleep. Rem, short/fast waves indicated brain activity is fairly high. Sometimes why REM sleep is called pareticold sleep, muscles in body are inhibited, brain activity is active, measured by EEG. If you wake someone up during REM, report detailed vivid dreams, a lot of visual imagery. Visual cortex, one area is active during REM SLEEP. Not to say that dreaming doesn't occur during non rem sleep, because there are reports of dreams during non rem sleep but not as often than during REM sleep. Reports in non rem tend to be vague and not detailed.
The physiology of appetite and sleep
how these behaviors are regulated by the body and brain. Two systems-important in maintaining our homeostatis or normal stable functioning of the body.
functions of sleep
hypothesis about why we need sleep or the functional significance of sleep is. Sleep probably originally evolved in animals as a means of energy conservation, conserving the bodies energy at times when it would not be beneficial to be active. For example, many animals such as squirrel for example go into hibernation at times when food is not as available in the environment, adaptive for the organism to be running around expending its energy , more adaptive for the organism to decrease its activity, decrease its body temperature so it can conserve some of that metabolic energy.
Sleep deprivation and emotional brain reactivity
implications for how the brain reacts or responds to emotional stimuli. Figures from 2009 article, observe that sleep deprivation induces a hyper limbic response in the amygdala to negative emotion stimuli. Measure brain activity in non sleep deprived and sleep deprived individuals in response to showing then pictures of negative events, like car accidents, war images, under conditions of sleep deprivation, amygdala response to those negative emotional stimuli, 60% greater, measured by FMRI. Amplified amygdala response you see with sleep deprivation is associated with a decrease in connectivity between amygdala and prefrontal cortex, prefrontal cortex-, area in the brain involved in executive function, impulse control, prefrontal normally serves to inhibit the amygdala, prefrontal cortex has a top down inhibitory function on the limbic system
Physiological response to stress
in addition to stimulations in the sympathetic NS, second major system that is activated by stress, hypothalamic-pirtuary-adrenal axis OR HPA axis. HPA axis, originates in hypothalamus, hypothalamus major hormonal center so it releases a lot of different hormones. When a stressful stimulus activated NS, causes neurons in the hypothalamus to release a hormone called CRH which stands for corticotripin-releasing hormone. CRH stress hormone released by hypothalamus in response to stress. CRH released by hypothalamus, going to travel down to the pituitary gland which is located right below the hypothalamus. That CRH is going to cause the pituitary gland to release a second hormone called ACTH which stands for Adrenocorticotropic hormone. ACTH hormone secreted by the pituitary gland in response to that CRH from the hypothalamus. That ACTH enter the bloodstream, enters the general circulation, travel through bloodstream all the way to the adrenal glands which sit on top of the kidneys. That ACTH causes the adrenal glands to release another hormone called cortisol. Cortisol, stress hormone that is released by the adrenal glands in response to that ACTH, hormone cascade that occurs whenever we experience a stressful stimulus, starts in hypothalamus and ultimately is going to result a release of cortisol in the adrenal glands. Cortisol, hormone acts many different cells in the body to increase glucose metabolism. Cortisol is classified as a glucocorticoid, increases blood glucose levels, contribute to this mobilization of energy that is part of the stress response. Prepare the body for action.
Sleep deprivation also induces a variety of cognitive impairments
in attention, memory. Preclinical animal work has shown, inhibits long term potentiation in the hippocampus, consistent with some of these detrimental effects on memory.
Hypothalamic regulation of appetite
mechanisms that are involved in regulating appetite and feedings behavior. Appetite regulation is really a product of communication between the digestive system and the brain. Communication between the digestive system and the brain determines when we eat and how much we eat. Our digestive system is able to detect information about what the energy needs of the body are and the digestive system sends signals to brain areas that are involved in controlling appetite, can make an appropriate response. Either increasing our decreasing our food intake to maintain an energy balance in the body. Make sure we have enough nutrients to be able to function. Digestive system communicates that information to the brain in large parts by releasing a number of different hormones into the blood stream. Those hormones travel through the blood to the brain and act on appetite control centers in the hypothalamus-brain area that most directly involved in regulating appetite and eating.
Exercise also increasing angiogenesis
increased blood supply to cells, bring in more oxygen, more nutrients to the cells. Exercise increases both neurogenesis and specific areas of the brain like hippocampus and increase angiogenesis, blood supply to cells. Certain practices like mindfulness, cognitive reappraisal, basically involved reterpreting the meaning of negative stimuli, those practices are associated with reduced emotional responses to negative events. Associated with increased cognitive control of emotion. Both cognitive therapy, cognitive behavioral therapy, meditation, both been shown in imaging studies to increase the functioning of the prefrontal cortex. Shown in several FMRI studies. Successful cognitive therapy and mediation increase the functioning of those prefrontal cortical structures, involved in regulating emotional response of the limbic system. Important point, response to the stressful event, critical. Its your response to the event that is important, that will determine if the psychological stress response gets activated. Primates, like us, have this huge cortex, has all of these descending connections down into the limbic system, by just thinking a though, thinking a negative thought can activate our stress response. Mediated by all of these connections between the cortex and limbic system. Conversely, thinking positive thoughts inhibit the stress response. Prominent future of our species, not necessarily unique to our species, primates, we have this huge cortex, able to activate the limbic system stress response just by what were thinking. Conversely, inhibit that stress response by what you think as well. Actual brain changes that are associated with these processes.
Type 1 diabetes
involves deficiency in insulin levels, body does not produce enough insulin. Have to take insulin shots
Another hormone in the short term regulation
is insulin. Hormone released by pancreas. Specifically by beta cells in pancreas. Major stimulus that causes insulin levels to rise, increase in blood glucose levels. When we start eating during the obsorbmative phase of metabolism, our blood glucose will start to go up. Increase in blood glucose levels stimulate the pancreas to start releasing insulin, rise in blood glucose stimulates insulin release from the pancreas. Insulin, critical hormone, allows glucose to enter the cells in the body, function of insulin. Need insulin for glucose to get transported into cells in your body so that glucose can be used for fuel. Without insulin, glucose cant get into your cells. Insulin binds to insulin receptors on the cells, allow glucose to be transported into the cell by glucose transporters.
Effects of cortisol on the body
it suppresses the immune system, has immunosuppressant effects, suppresses the immune system. Example, suppressed tissue inflammation in the body, part of the bodies response to some type of injury. This suppression of immune system by cortisol, actually be beneficial in short term, when your responding to acute stressor because the body is not devoting resources, not devoting immediate resources to repairing itself, tissue repair when it really needs to devote those resources to first respond to the threat and then repair itself later. This suppression of the immune system by cortisol may actually be beneficial in the short term, but under conditions of chronic stress, when you have got constantly high levels of cortisol in the body, prolonged suppression of the immune system, that chronic stress has been shown to increase the risk of getting sick, for developing infections like cold or flu, or in can increase duration of those illnesses. Have a sense based on our own experience, more likely to get sick when we are stressed out. Chronic stress has been shown in animal and human studies to increase the rate of disease progression. Example, progression of HIV into full blown AIDS. Increases the rate of tumor progression with different types of cancer. Chronic stress also exarberates disease progression. Also, several studies shown prolong stress increases the time for the body to heal after some type of injury has occurred. Did a study on, well known study with dental students, small lesion inside the mouth of students during a normal typical time of the semester and also did the same during finals week. Final exam week, measured the length of time for those wounds to heal, significantly greater during finals week so at a time when the students were under a lot of stress. Chronic stress shown in a number of studies to increase the time for wound healing. All of these effects that mentioned, believed to be mediated by a decrease in the bodies natural immune response during times of stress. Include in decrease of number of different types of immune system cells that are responsible for fighting infection. Decrease in natural killer cells, T cells, total white blood cells, lymphocytes. All of these types of cells, immune system cells, attack foreign microbes in the body. Mechanism that is believed to mediate many of the effects.
Another hormone , discovered 20 years ago, 1994. hormone is involved in the long term regulation of feeding behavior. Involved long term regulation of body fat.
leptin- hormone that is released by fat cells, released by adipose tissue into bloodstream. Also acts on hypothalamus to regulate food intake. Leptin receptors located in arcuate nucleus in the hypothalamus which leptin binds to. Leptin communicates to the brain, information about the bodies fat stores, communicates info to the brain about how much energy the body has stored as fat. Normal function of this hormone is to maintain body fat homestatis, to maintain our body fat levels when an appropriate range, to provide energy needs of the body. Normal conditions, don't want body fat to be too high or low. Leptin, regulates body fat homestatis. When the level of fat in body increases, increased leptin secretion. More fat cells, more leptin secretion. Leptin signals the hypothalamus, enough fat stores in the body. Results in decrease in appetite and food intake. Basically feed back system to your fat cells to your brain. Under normal conditions, increase levels leptin decrease food intake. The body communicating to the body, hey I have enough fat reserved down here, don't need to eat more. Conversely, when the level of fat in body is low, not as much adipose tissues, leptin secretion will be low, stimulates appetite and food intake, body signaling to the brain, fat stores are getting low, need to eat more. Important in maintaining energy homestatis in the body specifically by regulating the amount of body fat within appropriate levels.
certain eating disorders
like obesity, related in disfunction in these normal homeostatic mechanisms that control feeding. Hormonal feedback systems between body and brain, major mechanism that regulates appetite, not the only mechanism. Physical signals that are sent up from gut to brain, information about stomach destention, transmitted by Vagus nerve. Learning mechanism that control what we eat. Certain type of foods that activate reward pathways in the brain, sugar and fat both activate dopamine release. These hormonal feedback mechanisms-body communicates with they hypothalamus are critical in regulating our food intake. Jeff- Discovered leptin back in 1994- hormonal feedback systems work to regulate body weight.
Data from these FMRI
normal top down inhibitory function of the prefrontal cortex is impaired with sleep deprivation which maybe producing the hyper limbic response. So activity in the prefrontal cortex is altered, it will effect the amygdale, because those two brain areas are functionally interconnected.
Typical pattern of sleep-diagram
occurs during typical nigh in young adult in terms of different stages of sleep brain goes through during the night. Brain doesn't maintain steady activity throughout the night, goes on roller coaster ride, which is cycles through periods of decreased and increased activity. When you first go to sleep at night, enter stage 1 sleep then you progress through stages 2, 3, 4, into the deeper stages of sleep, after an hour of being asleep, brain starts to cycle back from stage 4 into the lighter stages of sleep again. Back through stages through 3 and 2 and then into the first REM episode, occurs about 90 minutes into sleep cycle. Dark blue bars-represent periods of REM sleep. Brain continues follow that general pattern through the night, non rem then rem, non rem then rem. Cycles occur approximately an hour and half or 90 minutes. Some differences throughout the night in terms of the amount of time we spend in different phases of sleep. First part of night-slow wave sleep occurring, spend more time in stages 3 and 4, deeper stages of sleep, first part of time. Night progresses, spent less time in slow wave sleep and more time in REM SLEEP during the later part of the night. REM episodes are longer. Almost half of the night REM sleep occurs during early morning hours. function of REM SLEEP, not well understood, hypothesis, activity that occurs in the brain during REM, maybe important in memory consolidation and memory processing for events that occur during the day. Same hypothesis for non rem sleep, don't really know for sure why this particular phase of sleep exists, why we cycle through rem episodes during the nights, characterize with EEG, still a lot of questions about the function of REM and NON REM sleep.
Short term regulation
one of the appetite regulating hormones. Discovered in last 15 years, new. Ghrelin-hormone that is released by the stomach, cells of the stomach. Acts on hypothalamus to stimulate appetite or increase appetite. Ghrelin considered hunger signal. Ghrelin levels go up or rise when we are in a fasting state, haven't eating in a while or stomach is empty, Ghrelin levels will be high. Conversely levels drop after eating. Levels of this hormone change as the energy state of the body changes. Haven't eaten for a while, stomach is empty, ghrelin levels increase, signal hypothalamus to generate a feeding response to help maintain or energy homestatis. Then after we eaten, ghrelin levels, so the hunger signal of hypothalamus goes down. Ghrelin, one of the preferial hormones, really important in the short term regulation of feedings. Levels of this hormone, go up and down throughout the day depending upon the state of digestive system. For example, late afternoon or late evening, before dinner, ghrelin levels will be pretty high if you haven't eaten for a while then go down after you eat.
Causes that faulty negative feedback system
one of the hypothesis, deficits in the negative feedback system in depressed individuals, maybe due to decrease number of glucocorticoid receptors in the hippocampus. If you don't have enough glucocorticoid receptors in hippocampus, then cortisol cannot activate that feedback system effectively, stress hormone levels will remain high. Deficit in brain glucocorticoid receptors, one source of the problem. Evidence that supports this, antidepressants treatment like SSRIs, shown in several studies increase glucocorticoids receptors in the hippocampus, decrease stress hormone levels. Part of the mechanism by which antidepressant treatments appear to be working, restoring that negative feedback system which normalizes HPA activity.
Consequences of sleep deprivation
physiology of the body, sleep deprivation, one obvious consequence induce excessive daytime sleepiness .
Autonomic nervous system
primary system that is activated when experience a stressor, part of nervous system that controls all glands, muscles, and internal organs on the body that we don't have voluntary control over it, heart, lungs, digestive system etc. includes all nerves that innervate those structures and control there functioning. Distinct from the somatic nervous system, somatic included all of those neurons that innervate the skeleton muscle and that control voluntary movement. Autonomic system-rather controls involuntary functions, controls heart rate constriction of the blood vessels, controls our digestive muscles and so forth.
type 2 diabetes
problem is primarily with insulin sensitivity, insulin resistance, body produces insulin but those insulin receptors have lost some of their sensitivity to the hormone. Glucose has greater difficultly getting into the cell to be used for fuel. If you have a fasting increase in blood glucose levels, elevated blood glucose level at a time when they shouldn't be elevated , indicate that you have a deficiency in the functioning of insulin in the body. Be a sign of pre diabetes. If you have fasting elevation in your blood glucose levels. Insulin also a hormone that is monitored by the arcuate nucleus of the hypothalamus, acts to inhibit appetite. Can be considered to be a satiety signal. After you have eaten, when blood glucose levels goes up, insulin levels are increased, signal hypothalamus to stop eating. Also another hormone, jus been discovered. Acts on hypothalamus to inhibit appetite, hormone also serves a satiety signal, hormone called peptide YY, PYY. Hormone released by the intestines, by cells in small and large intestines. Released after we eat, levels of this hormone also go up when we inject a meal. PYY acts on arcuate nucleus of the hypothalamus to decrease appetite. PYY has appetite suppressant effects. If you inject into a rat or human, decrease appetite. Sattidy signal. Attempts to use PYY as a weight loss drug by pharma companies, use this to potentially treat obesity, don't know the current status, not that simple to just inject a hormone to suppress appetite. Body will develop resistance to those hormones.
Number of environmental factors are more under our control
related to the ability to successfully adapt to stress. Social support, shown to be associated with activation of brain reward circuits like dopamgengic system. Also results in the increase release of certain hormones like oxytocin, promotes social attachement, reduces fear responses. Oxytocin receptors located in the amygdala, oxytocin binds to those receptors, reduces amygdala activity. Psyhcological effects of positive social interactions that help minigate stress, promote resilience to stress. Social support has direct effects on the brain, direct psychological effects. Adequate sleep, promotes resilience, how sleep deprivation amplify the amygdala response to negative stimuli. Conversely when you get adequate sleep, helps reduce the hyperactivity in the amygdala. Good nutrition and exercise, help maintain the normal functioning of all of the cells in the body including the brain. Exercise, major factor that has been shown to promote neurogenesis in the hippocampus or the production of new neurons in the hippocampus. Exercise increases levels of certain neurotripphins like BTNF, brain derived neurotrphic factor. Those neurotriphines help promote the production of new neurons. Promotes a healthy hippocampus.
Data is consistent with what we all know to be truth
short tempered, fly off the handle about minor things, angry more easily. Sleep deprivation effects the brains response to emotional stimuli. Consequences for aggressive behavior, depression, anxiety. All of those involve hyperactivity of the limbic system which is worsened by sleep deprivation.
Another hypothesis about function of sleep in which is related
sleep serves a restorative function in body and brain. For example, growth hormones secretion peaks during sleep, involved in building and repairing body tissue. Also certain neurotransmitters in the brain which may be replenished at night when certain brain systems are allowed to rest, so the neurotransmitters level is not continuously being depleted by activity. Another major hypothesis, important in learning and memory processing, number of studies that sleep deprivation has detrimental effects on cognitive performances. Impairs attention, impairs learning rates, impairs performance on memory tasks. Why you shouldn't deprive yourself of sleep before you take an exam even if its tempting to pull an all nighter. Sleep deprivation is detrimental effects on memory processing.
Acute and chronic stress
stress response that occurs which involves activation of the sympathetic and HPA axis, again it is a adaptive response in the short term, when were exposed to some type of acute stressor like taking an exam or responding to some acute physical threat. Those are situations we want to have plenty of glucose and blood and oxygen to support mental and physical activity. Again, this is not a system that was designed to be on all of the time. When stress is prolonged, chronic, have constantly have sympathetic activation, have constantly elevated levels of cortisol in the body, that is what produces damaging effects. Damaging effects of chronic stress, they have been characterized in three major domains, determential effects of chronic stress on immune system, cardiovascular system and the brain, CNS effects.
Two major divisions of the autonomic nervous system
sympathetic and parasympathetic branches. Opposite functions. Sympathetic brand-activated when we experience some type of stressful stimulus. Activation of the sympathetic system results in increase in heart rate, increase blood pressure, increase in oxygen uptake by the lungs. Increase glucose release from the liver. All of the things that mobolize the body to be able to respond to a threat. Sympathetic meditates fight or flight responses, prepare the body for activity by mobilizing energy resources. Important, not all of the effects of sympathetic activation are excitatory, some of the sympathetic effects are inhibitory. Example, activation of the sympathetic nervous system, it inhibits reproductive function. Inhibits ovulation, sexual arousal, digestion because when the body needs to respond to acute threat, not the time to devote resources to reproduction or digestion, mobilize some processes at the expense of others like digestion and reproduction, allow the body to maximize efficiency in responding to a threat.
Pass from waking state through
these 4 stages of sleep, gradual progression from short/fast waves which indicate an activated cortex to these longer/slower waves which are deep sleep. Four sleep stages, 1 through 4-collectivly referred to non rem sleep, to distinguish them from REM sleep, REM, distinct phase of sleep, rapid eye movement, rapid movement of eyes behind eye lids during REM, also lose of muscle tone in the body, during rem sleep, large muscles in body are inhibited from moving, inhibitory signals from brain stem that inhibit motor neurons in the spinal cord during REM sleep, rapid eye movement and muscle atonia are lack of muscletone, characterizes of rem sleep that you don't see in the other four stages of sleep.
Leptin
was discovered by studying a strain a mouse, genetically obese. OB/OB mouse. Much heavier than typical mouse. Genetically obese mice poses a defect in a single gene that gene encodes for leptin , these mice do not produce leptin because they have a defect in that gene. Leptin deficient. Lack leptin, no signal for their body to tell their body that fat levels are okay, tell their brain, fat levels are adequate. Brains of these mice think their starving, overeat, become very obese. Event though they have a huge amount of fat, information about body fat level cant get communicated to the brain, those fat cells don't release leptin, don't produce that signal. No feedback to their brain to tell that there is enough fat in the body.
Same argument has been extended for other species including humans
we live in a physical environment where were exposed to crates of light and dark everyday, times where its not efficient to be active especially at night, especially because we rely heavily on our vision. One of the hypothesis about the function of sleep.
regulation of HPA activity
what regulates the activity of the HPA axis. Limbic regulation of the hypothalamus. Some of the stress related disorders like depression, associated with altered HPA activity. Believed to be due to dysregulation of the HPA axis. Encounter a stressful stimulus, sensory input to the brain, some type of threat in the environment, one of the primary structures that is activated in the brain is amygdala, threatening stimuli activate the amygdala. Limbic structure, important in processing emotion. Particularly negative emotion. Processes information about fearful stimuli. Amygdala, sends axons to the hypothalamus, sends projections to the hypothalamus to those neurons in the hypothalamus that release CRH. When amygdala gets activated by some type of threat, cause the cells in the hypothalamus to release CRH. Exitory connection between amygdala and hypothalamus, stressful stimuli activate amygdala, then in turn activate the HPA axis. Stimulation of HPA axis, result in hormonal cascade, release of cortisol into the bloodstream. Act to increase blood glucose levels, prepare the body to respond to a stressor. Also, a feed back mechanism, by which the brain monitors how much cortisol is in the blood stream, one place the cortisol is going to travel back to the brain to the hippocampus, the hippocampus contains a lot of glucocorticoid receptors. Vey high concentration of glucocorticoid receptors on hippocampal neurons. Activation of the hippocampus by cortisol, part of a negative feedback system that regulates HPA activity. Hippocampus sends projections to the hypothalamus, but those projections from the hippocampus to the hypothalamus are inhibitory, they inhibit CRH release. Acivation by the hippocampus by cortisol, inhibit HPA activity. Inhibit CRH release from the hypothalamus. Brain has this negative feedback system that monitors cortisol levels in the bloodstream. Reduces HPA activity when cortisol levels are high. Eventually, the body needs to return to homestatis after a stressor is over and this negative feed back system, one mechanism that helps regulate that. Want to be able to respond to the stressor but when stress is over, shut the system off.
hormones
where their released in the body and how they act to influence appetite.
inject these mice
with leptin, leptin replace treatment, can reverse their obesity. Genetically obsese mice-treated with leptin, restore that leptin signal to hypothalamus, decrease appetite and food intake. Mouse returns to a more normal weight. When leptin was discovered-pharma was all over it, though it was a way to reverse human obesity. Magic bullet.
