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<b><div>Stages of Cognitive and Emotional Regulation</div></b>"<b><div><span style=""font-weight: 400; text-decoration-line: underline;"">1) What’s happening?</span></div><ul><li><div><span style=""font-weight: 400;"">Sensation, Perception, Cognition</span></div></li><li><div>Occipital, Parietal, Temporal, and Frontal lobes</div></li></ul><div><span style=""font-weight: 400; text-decoration-line: underline;"">2) Is it dangerous</span></div><ul><li><div><span style=""font-weight: 400;"">Primary appraisal</span></div></li><li><div><span style=""font-weight: 400;"">Amygdala (by itself = low road to fear)</span></div></li><li><div><span style=""font-weight: 400;"">Fronto-limbic connections (amygdala with </span></div></li><li><div><span style=""font-weight: 400;"">Connections between prefrontal lobes and the limbic system</span></div></li><li><div><span style=""font-weight: 400;"">Emotion appraisal more associated with dorsal prefrontal (dPFC, dACC)</span></div></li></ul><div><span style=""font-weight: 400; text-decoration-line: underline;"">3) How should I react?</span></div><ul><li><div><span style=""font-weight: 400;"">Secondary Appraisal </span></div></li></ul><ul><li><div><span style=""font-weight: 400;"">Fronto-limbic connections </span></div></li><li><div><span style=""font-weight: 400;"">Emotion regulation more associated with ventral prefrontal (vPFC, vACC)</span></div></li></ul><div><span style=""font-weight: 400; text-decoration-line: underline;"">4) Am I doing ok?  </span></div><ul><li><div><span style=""font-weight: 400;"">What should I do/feel/think next?</span></div></li><li><div><span style=""font-weight: 400;"">Coping Behaviors</span></div></li><li><div><span style=""font-weight: 400;"">Central Feedback System</span></div></li><li><div><span style=""font-weight: 400;"">Fronto-limbic connections with hypothalamus and brainstem feedback</span></div></li></ul></b>"
What’s Happening?"<b><div><span style=""font-weight: 400;"">Any “awareness” or “knowledge” requires </span></div><div>Sensation and Perception</div><ul><li><div><span style=""font-weight: 400;"">Sensory info sent to</span><span style=""font-weight: 400;""> thalamus</span><span style=""font-weight: 400;""> (Sight, sound, touch, taste (but not smell))</span></div></li><li><div>Thalamus relays info to primary receiving areas<span style=""font-weight: 400;""> </span></div></li><ul><li><div><span style=""font-weight: 400;"">In Occipital, Temporal, and Parietal lobes</span></div></li></ul></ul><ul><li><div><span style=""font-weight: 400;"">Primary receiving areas relay info to association areas</span></div></li><ul><li><div><span style=""font-weight: 400;"">Connections between and within the four lobes</span></div></li></ul><li><div><span style=""font-weight: 400;"">Sensory info converted into meaningful perceptions</span></div></li><ul><li><div><span style=""font-weight: 400;"">Color, shape, motion – “my grandmothers face” “the blue dress on the right”, etc etc...</span></div></li></ul><li><div><span style=""font-weight: 400;"">Perceptual info sent to frontal lobes and limbic areas</span></div></li><li><div><span style=""font-weight: 400;"">Cognitive perceptions can activate affective feelings</span></div></li></ul></b>"
Emotional Appraisals"<div style=""font-weight: bold;""><span style=""font-weight: 400;"">How we interpret a situation will govern how we respond emotionally</span></div><ul style=""font-weight: bold;""><li><div><span style=""font-weight: 400;"">Appraisals of danger → fear</span></div></li><li><div><span style=""font-weight: 400;"">Appraisals of fun and safety → happiness</span></div></li></ul><div style=""font-weight: bold;""><span style=""font-weight: 400;"">Appraisals are often described as the cognitive component of our emotions</span></div><ul style=""font-weight: bold;""><li><div><span style=""font-weight: 400;"">What we “think” about the situation, will influence how we “feel” about it. Both, our thoughts and feelings will influence what we “do” about it</span></div></li></ul>"
<div>Psychological vs. Physical Stress</div>"<b><div>Physical Stress<span style=""font-weight: 400;"">= Requires activation and physiological arousal to meet physical demands</span></div><div><span style=""font-weight: 400;"">Cannot run or lift a heavy weight without increasing physiological arousal </span></div><div><span style=""font-weight: 400;"">Physical stressors involve psychological aspects</span></div><div><span style=""font-weight: 400;"">The valence of the stressor may be positive, negative, or neutral. Whether you’re running for fun, or running for your life</span></div><div><span style=""font-weight: 400;"">Either requires increased physiological arousal </span></div><br><div>Psychological Stress<span style=""font-weight: 400;"">= Does not require activation to meet physical demands</span></div><ul><li><div><span style=""font-weight: 400;"">Taking an exam is stressful, but you can do it sitting on your butt</span></div></li></ul><div><span style=""font-weight: 400;"">However, psychological stressors can still cause physiological arousal</span></div><div><span style=""font-weight: 400;"">More aversive (negative valence) stressors produce feelings of threat</span></div><div><span style=""font-weight: 400;"">More pleasant (positive valence) stressors produce feelings of challenge </span></div></b><br>"
<div>Categories of Emotional Appraisals</div><div>Threat (Distress), </div><div>Challenge (Eustress)</div><div>Benign or Irrelevant</div>
Emotional Appraisal: Threat (Distress) <div>Stressor is dangerous or overwhelming </div><div>Requires activation, negative valence (aversive)</div><div>Sympathetic activation with large increase in cortisol (HPA axis)</div>
Emotional Appraisal: Challenge (Eustress)<div>Stressor may be engaging or rewarding</div><div>Requires activation, positive valence (appetitive)</div><div>Sympathetic activation with minor increase in cortisol</div>
Emotinal Appraisal: Benign or Irrelevant<div>”Stressor” is not stressful.  May be harmless or pleasant (Benign)</div><div>”Stressor” does apply to self, even if it’s aversive to others (Irrelevant)</div><div>Does not require activation.  </div><div>Parasympathetic nervous system. Return to homeostasis.</div>
<div>Implicit Appraisals</div>"<b><div><span style=""font-weight: 400;"">Emotional appraisals do not have to be fully conscious</span></div><ul><li><div><span style=""font-weight: 400;"">Appraisals may be implicit due to past experiences and conditioning</span></div></li></ul><br><div><span style=""font-weight: 400;"">Classical conditioning</span></div><ul><li><div><span style=""font-weight: 400;"">A stimulus that was initially neutral, gets paired with a stimulus that evokes an emotional response</span></div></li><li><div><span style=""font-weight: 400;"">Later the stimulus that was neutral, now evokes that some emotional response</span></div></li></ul><br><div><span style=""font-weight: 400;"">Classical conditioning does not require conscious awareness</span></div><ul><li><div><span style=""font-weight: 400;"">Individuals with severe amnesia can still learn from classical conditioning</span></div></li><li><div><span style=""font-weight: 400;"">Damage to hippocampus does not interfere with conditioning </span></div></li></ul></b>"
<div>Conscious vs. Unconscious Memories</div>"<b><div>Hippocampus involved in conscious and explicit memories (declarative memories)</div><br><div>Amygdala involved in “affective memories”<span style=""font-weight: 400;"">= responds to situation requiring motivational states (emotions)</span></div><ul><li><div><span style=""font-weight: 400;"">Known for processing fearful responses, but involved in positive emotions too</span></div></li><li><div><span style=""font-weight: 400;"">Fear is just a very intense motivational state</span></div></li><li><div>Classical conditioning is possible without a hippocampus, but not without the amygdala</div></li></ul></b>"
<div>Emotional Appraisals: Primary Appraisals</div>"<b><div><span style=""font-weight: 400;"">influenced by personal relevance, cognitive beliefs, and behavioral commitments</span></div><ul><li><div><span style=""font-weight: 400;"">Biased towards searching for threatening information</span></div></li><li><div><span style=""font-weight: 400;"">Types of primary appraisals:  Threat, Challenge, Benign, or Irrelevant </span></div></li></ul></b>"
<div>Emotional Appraisals: Secondary Appraisals</div><div>How to respond to or how to cope with the situation </div><div>What will be required? What resources are available?  </div>
Problem-Focused coping"<b><div><span style=""font-weight: 400;"">Coping based on trying to solve the problem causing stress</span></div><ul><li><div><span style=""font-weight: 400;"">Involves trying to understand the problem, devise a strategy to deal with it </span></div></li><li><div>Pros<span style=""font-weight: 400;"">: May ”solve” the problem.  Lessen, minimize, or avoid future stress</span></div></li><li><div>Cons<span style=""font-weight: 400;"">:   May be initially costly in time, energy, and resources</span></div></li></ul></b>"
Emotion-Focused coping<div>Coping based on dealing with the emotional feeling of stress</div><div>Involves trying to limit the emotional reaction</div><div>May involve avoidance, denial, acceptance, venting, or blame</div><div><b>Pros</b>:  Initially less costly </div><div><b>Cons</b>:  The problem isn’t solved.  Drains coping resources over the long-term</div>
<div>Is it dangerous: Primary Appraisals</div>"<div><b><div><span style=""font-weight: 400;""> Immediate emotional interpretation</span></div><ul><li><div><span style=""font-weight: 400;"">Threat, Challenge, Benign, Irrelevant</span></div></li><li><div><span style=""font-weight: 400;"">Fronto-limbic connections</span></div></li><li><div><span style=""font-weight: 400;"">Can be conscious or unconscious</span></div></li><li><div><span style=""font-weight: 400;"">Prioritizes “threat” appraisals  (Fear)</span></div></li></ul></b></div>"
<div>Is it dangerous? LeDoux’s Low vs. high road to fear</div><div>Low road = Amygdala responds to sensory info without input from frontal lobes</div><ul><li><div>Reaction to sensory information</div></li><li><div><div>Sensory info sent from <b>thalamus</b> directly to <b>amygdala</b></div><div>Fast, unconscious processing</div><div>Quickly shifts attention to dangerous stimuli</div></div></li></ul><div>High road = Amygdala responds to sensory info after it was processed by frontal lobes</div><ul><li><div>Reactions to conscious perceptions</div></li><li><div><div>Sensory info first processed by  cortex,  then sent to amygdala</div><div>Slower, conscious processing</div><div>Allows for an emotional appraisal of the situation </div></div></li></ul>
Limbic System"<b><div>The “Emotional brain”</div><div><span style=""font-weight: 400; text-decoration-line: underline;"">The main areas</span><br></div><ul><li><div><span style=""font-weight: 400;"">Amygdala</span></div></li><li><div><span style=""font-weight: 400;"">Hippocampus</span></div></li><li><div><span style=""font-weight: 400;"">Hypothalamus</span></div></li><li><div><span style=""font-weight: 400;"">Thalamus</span></div></li><li><div><span style=""font-weight: 400;"">Cingulate Cortex</span></div></li></ul></b>"
<b><div>Important Limbic Areas: Hippocampus</div></b>"<b><div><span style=""font-weight: 400;"">Vital for Declarative Memory (Explicit Memory)</span></div><ul><li><div><span style=""font-weight: 400;"">Memories that can be consciously recalled </span></div></li><li><div>Connections to PVN of hypothalamus decrease HPA axis</div></li><li><div><span style=""font-weight: 400;"">Negative feedback when detecting cortisol</span></div></li></ul></b>"
<b><div>Important Limbic Areas: Amygdala</div></b>"<b><div><span style=""font-weight: 400;"">Vital for processing emotions and emotional memories</span></div><ul><li><div>Can create long-term implicit memories via classical conditioning </div></li><li><div><span style=""font-weight: 400;"">”Emotional memories’ may be learned at an unconscious level</span></div></li><li><div>Connections to PVN of hypothalamus increase HPA axis</div></li></ul></b>"
<div>Important Limbic Areas: “Extended Amygdala”</div>"<b><div><span style=""font-weight: 400;"">Amygdala + Nucleus accumbens – reward motivations</span></div><ul><li><div>BNST (bed nucleus of stria terminalis) - involved in stress, fear, mood, sexual response</div></li><li><div><span style=""font-weight: 400;"">A junction point between amygdala, hippocampus, hypothalamus, and brainstem nuclei</span></div></li></ul></b>"
<div>Amygdala Nucleii: Basolateral group </div>"<b><ul><li><div><span style=""font-weight: 400;"">Critical for classical conditioning</span></div></li><li><div><span style=""font-weight: 400;"">Associating neutral stimuli with emotion provoking stimuli</span></div></li></ul></b>"
Amygdala Nucleii: Central group"<b><ul><li><div><span style=""font-weight: 400;"">Critical for regulating the expression of fear</span></div></li><li><div><span style=""font-weight: 400;"">Including facial expressions (in primates)</span></div></li></ul></b>"
<div>Amygdala Nucleii: Medial group</div>"<b><ul><li><div><span style=""font-weight: 400;"">Plays role in evaluating responses to scents</span></div></li><li><div><span style=""font-weight: 400;"">In other species, used for social communications</span></div></li></ul></b>"
<div>Amygdala Connections</div>"<b><div><span style=""font-weight: 400;"">Frontal-limbic connections</span></div><ul><li><div><span style=""font-weight: 400;"">Limbic areas like amygdala and hippocampus connected to areas of the prefrontal lobe</span></div></li></ul><div><span style=""font-weight: 400;"">Amygdala also directly connected to the thalamus and hypothalamus</span></div><div><span style=""font-weight: 400;"">Amygdala also connected to brainstem </span></div><br></b>"
<b><div>Cortical Areas for Appraisals: Prefrontal Cortex</div></b>"<b><div>Dorsolateral (DLPFC)<span style=""font-weight: 400;""> = Conscious awareness.  Control of working memory</span></div><div>Medial (MPFC)<span style=""font-weight: 400;""> = Associations between emotions and context</span></div><ul><li><div><span style=""font-weight: 400;"">In humans, self-relevant info</span></div></li></ul><div>Ventromedial (VMPFC) <span style=""font-weight: 400;"">= Associated with “gut feelings”</span></div><div>Orbital (OPFC<span style=""font-weight: 400;"">)= Associated with emotional decision making.</span></div></b>"
"<span style=""font-weight: 700;"">Cortical Areas for Appraisals: </span><b>Anterior Cingulate Cortex (ACC)</b>""<b><span style=""font-weight: 400;"">Detects conflicts and Involved in decision making</span></b>"
<b>Cortical Areas involved in Appraisals Meta analysis </b>"<b><div><span style=""font-weight: 400;"">More dorsal areas of PFC and ACC associated with emotional appraisals and expression</span></div><ul><li><div><span style=""font-weight: 400;"">Evaluations of good vs. bad, challenge vs. threat</span></div></li><li><div><span style=""font-weight: 400;"">Feelings of happy, sad, fear, etc...</span></div></li></ul><div><span style=""font-weight: 400;"">More ventral areas of PFC and ACC associated with emotion regulation</span></div><ul><li><div><span style=""font-weight: 400;"">Selecting behavioral responses</span></div></li><li><div><span style=""font-weight: 400;""><b><span style=""font-weight: 400;"">Suppressing undesired behaviors</span></b><br></span></div></li></ul></b>"
<div>How Should I React? </div>"<b><div>Secondary Appraisals<span style=""font-weight: 400;""> = Re-interpretation of emotion (Your reaction to your reaction) </span></div><ul><li><div><span style=""font-weight: 400;"">Involves cognitive evaluations of initial emotion</span></div></li><li><div><span style=""font-weight: 400;"">Attempts to regulate emotional reactions</span></div></li><li><div><span style=""font-weight: 400;"">Plans about how to cope</span></div></li></ul><br><div><span style=""font-weight: 400;"">Fronto-limbic connections</span></div><div><span style=""font-weight: 400;"">Meta-analysis found ....</span></div><ul><li><div>Dorsal PFC and ACC<span style=""font-weight: 400;"">. -- emotion appraisal and expression</span></div></li><li><div>Ventral PFC and ACC<span style=""font-weight: 400;""> – emotion regulation</span></div></li></ul></b>"
Central Feedback Subsystem (CRF Feedback System)<div>Locus Ceruleus  → norepinephrine</div><div>Raphe Nucleus → serotonin</div><div>Ventral Tegmental Area (VTA) → dopamine</div><br><div>Receives inputs from the amygdala and hypothalamus</div><br><div>Sends feedback back to the limbic system and the prefrontal cortex</div><br>
<div>The Three Amigos: Locus Ceruleus</div>"<b><div><span style=""font-weight: 400;"">Main source of norepinephrine in the CNS</span></div><ul><li><div><span style=""font-weight: 400;"">Functions as a “global arousal system” </span></div></li><li><div><span style=""font-weight: 400;"">Most active when behaviorally active, awake, and alert</span></div></li><li><div><span style=""font-weight: 400;"">Inactive while asleep</span></div></li></ul></b>"
<div>The Three Amigos: Raphe Nucleii</div>"<b><div><span style=""font-weight: 400;"">Major source of serotonin</span></div><ul><li><div><span style=""font-weight: 400;"">Functions as a mood regulation system</span></div></li><li><div><span style=""font-weight: 400;"">Disruption of this system associated with mood disorders like anxiety and depression </span></div></li></ul></b>"
<div>The Three Amigos: Ventral Tegmental Area</div>"<b><div><span style=""font-weight: 400;"">Major source of dopamine</span></div><ul><li><div><span style=""font-weight: 400;"">Associated with attention, motivation, and reward</span></div></li><li><div><span style=""font-weight: 400;"">Addictive behavior associated with this system </span></div></li></ul></b>"
<div>What should I feel, think, or do next?</div>"<b><div>Coping Behaviors<span style=""font-weight: 400;""> = How we respond and adapt to the emotions</span></div><ul><li><div><span style=""font-weight: 400;"">Emotion-focused vs. Problem-focused coping</span></div></li><li><div><span style=""font-weight: 400;"">Should I feel something different?  Vs. should I do something different?</span></div></li></ul></b>"
<div>Hypothalamic-Sympathetic-Adreno-Medullary  (HSAM or SAM)</div><div>Regulated by dorsal and ventral PVN</div><div>Connects to brainstem</div><div>Projections to organs of SNS</div><div>Release of epinephrine and norepinephrine from medulla of adrenal gland</div>
<div>Hypothalamic-Pituitary-Adreno-Cortical (HPAC or HPA)</div><div>Regulated by medial PVN</div><div>Connects to pituitary </div><div>Release of cortisol from the cortex of adrenal gland</div>
<div>CRF Feedback System = Feed-forward processes</div><div>Each part must dynamically adjust to inputs from the other parts</div><div>Frontal lobes → limbic system → Hypothalamus → Brainstem</div><div>All parts contribute to the type and intensity of response</div><div>Response will vary depending on appraisals, motivations, arousal, and mood</div>
<div>HSAM (sympathetic activation)</div><div>Epinephrine and norepinephrine regulation</div><div>Two types of catecholamines</div><div>Adrenergic (related to adrenaline)</div><div>Aminergic (made from amino acids)</div>
<div>HPAC (HPA axis)</div>Cortisol regulation<br>Steroid hormone (made from cholesterol)<br><ul><li>Glucocorticoids Are cortisol (in humans) and other similar hormones (corticosterone in rats)</li></ul><div>The two systems work in harmony.... They talk to each other...and increase each other’s effects</div><br>
<div>Stress Hormones: Aminergi</div>"<b><div><span style=""font-weight: 400;"">Made from amino acids</span></div><div>Catecholamines<span style=""font-weight: 400;""> (made from the amino acid tyrosine)</span></div><ul><li><div><span style=""font-weight: 400;"">Epinephrine</span></div></li></ul><ul><li><div><span style=""font-weight: 400;"">Norepinephrine</span></div></li><li><div><span style=""font-weight: 400;"">Dopamine</span></div></li></ul><div><span style=""font-weight: 400;"">Serotonin (made from the amino acid tryptophan)Melatonin is derived from serotonin</span></div></b><br>"
<div>Stress Hormones: Steroid hormones</div>"<b><div><span style=""font-weight: 400;"">Made from cholesterol</span></div><div>Glucocorticoids = <span style=""font-weight: 400;"">Cortisol (in humans), Corticosterone (in rats)</span></div><ul><li><div><span style=""font-weight: 400;"">Has effects on most cell types in the body</span></div></li></ul><div><span style=""font-weight: 400;"">MineralocorticoidsMainly involved in regulating balance of water and electrolytes</span></div><div><span style=""font-weight: 400;"">Sex hormones </span></div></b>"
<div>Epinephrine vs.  Norepinephrine</div>"<b><div><span style=""font-weight: 400;"">Similar effects</span></div><div><span style=""font-weight: 400;"">Both act as excitatory neurotransmitters (in CNS and PNS)</span></div><ul><li><div>Norepinephrine involved in general arousal (in brain)</div></li><li><div>Epinephrine limited function as neurotransmitter (in brain)</div></li></ul><div><span style=""font-weight: 400;"">Both released from the adrenal medulla </span></div><div><span style=""font-weight: 400;"">Both increase heart rate, force of heart contractions</span></div><div><span style=""font-weight: 400;"">Both increase metabolic energy</span></div><ul><li><div><span style=""font-weight: 400;"">Increase blood sugar and release of fat stores</span></div></li></ul><div><span style=""font-weight: 400;"">Epinephrine more impact on heart and lungs</span></div><div><span style=""font-weight: 400;"">Norepinephrine more impact on blood vessels</span></div></b><br>"
<div>Adrenergic receptors: Alpha receptors</div>"<b><div><span style=""font-weight: 400;"">More activated by </span>norepinephrine</div><ul><li><div><span style=""font-weight: 400;"">Typically leads to Vasoconstriction (squeeze the blood vessels)</span></div></li><li><div><span style=""font-weight: 400;"">Can quickly increase blood pressure</span></div></li></ul></b>"
<div>Adrenergic receptors: Beta receptors</div>"<b><div><span style=""font-weight: 400;"">More activated by </span>epinephrine</div><ul><li><div><span style=""font-weight: 400;"">Typically leads to Vasodilation (relax the blood vessels)</span></div></li><li><div><span style=""font-weight: 400;"">Increases heart rate</span></div></li><li><div><span style=""font-weight: 400;"">Beta receptors on vagus nerve ultimately connect to amygdala </span></div></li><li><div><span style=""font-weight: 400;"">Amygdala gets feedback from sympathetic activation </span></div></li></ul></b>"
<div>Normal Cortisol Regulation</div>"<b><div><span style=""font-weight: 400;"">Cortisol is part of regular metabolism</span></div><ul><li><div><span style=""font-weight: 400;"">Circadian rhythm for cortisol production</span></div></li><li><div><span style=""font-weight: 400;"">Regulated by sleep-wake cycle, influenced by hours of “daylight”</span></div></li></ul></b>"
<div>Cortisol <b>permissive</b> role</div>"<b><div><span style=""font-weight: 400;"">normal levels of cortisol lets things happen</span></div><ul><li><div><span style=""font-weight: 400;"">“Maintain regularly scheduled program</span></div></li></ul></b>"
<div>Cortisol <b>productive</b> role</div>"<b><div><span style=""font-weight: 400;"">high levels of cortisol makes things happen</span></div><ul><li><div><span style=""font-weight: 400;"">“Shift focus to emergency tasks”</span></div></li><li><div><span style=""font-weight: 400;"">Certain metabolic functions get prioritized over others</span></div></li></ul></b>"
Circadian Rhythm of Cortisol Regulation<div>Suprachiasmatic nucleus (SCN) of hypothalamus</div><div>Receives visual info from thalamus</div><div>Day-night cycles detected from light exposure</div><div>SCN regulates daily activity of PVN</div>
<div>Morning to Night: <b>Functions of Cortisol</b></div>"<b><div><span style=""font-weight: 400;"">Cortisol is called a stress hormone, but is needed for normal homeostatic functioning</span></div><ul><li><div><span style=""font-weight: 400;"">Has a wide range of effects</span></div></li><li><div><span style=""font-weight: 400;"">Cortisol does not trigger a stress response.  It regulates the stress response</span></div></li><li><div><span style=""font-weight: 400;"">The presence of cortisol by itself should not be considered a sign of stress</span></div></li></ul></b>"
<div>Negative Feedback Loops With Cortisol</div>"<b><div>Cortisol is released into the bloodstream</div><ul><li><div><span style=""font-weight: 400;"">Detection of cortisol reduces production of cortisol</span></div></li></ul><div>At the pituitary</div><ul><li><div><span style=""font-weight: 400;"">Detection of cortisol, reduces production of ACTH</span></div></li></ul><div>At the hypothalamus</div><ul><li><div><span style=""font-weight: 400;"">Detection of cortisol in cerebrospinal fluid (third ventricle) Reduces activity of the medial PVN</span></div></li></ul><div>At the hippocampus</div><ul><li><div><span style=""font-weight: 400;"">Hippocampus can increase or decrease PVN activity, but detection of cortisol decreases PVN</span></div></li><li><div><span style=""font-weight: 400;"">Hippocampus important inhibitor of HPA axis </span></div></li></ul></b>"
<div>Cortisol During Stress</div>"<b><div><span style=""font-weight: 400;"">Stress decreases effects of negative feedback</span><br></div><ul><li><div><span style=""font-weight: 400;"">Increased cortisol should decrease production of CRF in the hypothalamus</span></div></li></ul><div><span style=""font-weight: 400;"">BUT.. other players involved....</span></div><ul><li><div><span style=""font-weight: 400;"">Amygdala</span></div></li><li><div><span style=""font-weight: 400;"">CRF Feedback system </span></div></li><li><div><span style=""font-weight: 400;"">others including the immune system</span></div></li></ul></b>"
<div>More ways to regulate cortisol</div>"<b><div><span style=""font-weight: 400;"">1) “Normal” Cortisol regulation</span></div><ul><li><div><span style=""font-weight: 400;"">Daily cycles of cortisol release</span></div></li><li><div><span style=""font-weight: 400;"">Negative feedback regulation </span></div></li></ul><div><span style=""font-weight: 400;"">2) Stress induced cortisol regulation</span></div><ul><li><div><span style=""font-weight: 400;"">Produced by extreme or prolonged stress when HSAM and HPAC remain simultaneously active</span></div></li><li><div><span style=""font-weight: 400;"">Not easily regulated with negative feedback</span></div></li><li><div><span style=""font-weight: 400;"">Allows cortisol levels to increase beyond “normal” levelsBut Wait... There’s More</span></div></li></ul></b>"
Ways to the HPA: Parvocellular (smaller cells)<div>Release CRF alone</div><div>Normal homeostasis</div><div>Less effect on ACTH release</div><div>More responsive to negative feedback (turns off when cortisol is detected</div>
Ways to the HPA: Magnocellular (bigger cells)<div>Releases CRF with Vasopressin (CRF-AVP)</div><div>Causes more ACTH release</div><div>Ten times less responsive to negative feedback  Two ways to the HPA </div>
Regulating HPA: Parvocellular neurons of the PVN  (CRF neurons)<div>Smaller neurons in the paraventricular nucleus</div><div>Controls normal level of cortisol secretion </div><div>Release CRF into pituitary --> pituitary releases ACTH</div><div>Easily regulated by negative feedback loops</div>
Regulating HPA: Magnocellular neurons on the PVN  (CRF-AVP neurons)<div>Bigger neurons in the paraventricular nucleus</div><div>Release CRF with Vassopressin</div><div>Connections to pituitary to release ACTH</div><div>Connections to brainstem (aminergic nuclei)</div><div>Triggered by sympathetic activation </div><div>Not easily regulated by negative feedback loops</div>
<div>Minor Stressors</div><div>Sympathetic activation (threat or challenge)</div><div>SAM signals activation of the HPA</div><div>If stress is short-term, sympathetic turns off quickly</div><div>HPA regulation returns to “normal” circadian cycle</div><div>HPA return to baseline takes longer than SAM return to baseline</div>
Major Stressors<div>Extreme or extended stressor</div><div>SAM and HPA may remain simultaneously active for extended time</div><div>Effects of both are intensified</div><div>Activates CRF feedback system throughout brain</div><div>Activates Magnocellular (CRF-AVP) neurons of the PVN </div><div>PVN less responsive to negative feedback</div>
<div>Activation of Magnocellular neurons of PVN</div>"<b><div><span style=""font-weight: 400;"">Extreme Stressors... </span></div><ul><li><div><span style=""font-weight: 400;"">Triggers the magnocellular neurons of PVN  </span></div></li><li><div><span style=""font-weight: 400;"">CRF released in combination with Vassopressin</span></div></li><li><div><span style=""font-weight: 400;"">More ACTH is released</span></div></li><li><div><span style=""font-weight: 400;"">HPA activity becomes less responsive to negative feedback</span></div></li></ul><br><div><span style=""font-weight: 400;"">Therefore...levels of cortisol increase beyond “normal” levels</span></div><ul><li><div><span style=""font-weight: 400;"">High levels of cortisol signal need to activate new systems</span></div></li></ul></b>"
Amygdala regulating HSAM<div>Monitors sympathetic activity  through vagus nerve</div><div>Vagus nerve has beta-adrenergic receptors that detect epinephrine</div>
<div>Amygdala regulating HPAC</div><div>Cortisol passes blood-brain barrier, so amygdala can directly monitor levels of cortisol</div><div>Amygdala “knows” when HSAM and HPAC are both higher than normal </div>
<div>Type 1 (MR) Cortisol receptor</div><div>Sensitive to low levels of cortisol</div><div>Regulates daily cycle of cortisol</div>
<div>Type 2 (GR) Cortisol receptor</div><div>Much less sensitive to cortisol</div><div>Only active when cortisol levels are very high </div><div>Regulation of stress responding </div><div>Can alter gene expression </div>
Hippocampus and hypothalamus contain what cortisol receptors? both Type 1 and Type 2
Amygdala and frontal lobe areas contain what type of cortisol receptors? Mostly type 2
<div>Amygdala is Sensitive</div>"<b><div><span style=""font-weight: 400;"">Amygdala primarily has Type 2 (GR) cortisol receptors</span></div><ul><li><div><span style=""font-weight: 400;"">So...amygdala can recognize states of high stress in the body</span></div></li></ul><br><div>Type 2 (GR) Cortisol receptors</div><ul><li><div><span style=""font-weight: 400;"">Only sensitive to high levels of cortisol</span></div></li><li><div><span style=""font-weight: 400;"">Only activated when stress levels are high </span></div></li><li><div>Can alter gene expression....</div></li></ul><br><div>Activation of Type 2 (GR) receptors can produce long-term changes</div></b><br>"
<div>Sensitizing the Amygdala</div>"<b><div><span style=""font-weight: 400;"">Amygdala can be “sensitized” to stress</span></div><ul><li><div><span style=""font-weight: 400;"">Demonstrated with infusions of corticosterone into the rat amygdala </span></div></li></ul><div><span style=""font-weight: 400;"">When glucocorticoid levels are unusually high....</span></div><ul><li><div><span style=""font-weight: 400;"">Activation of Type 2 (GR) receptors in amygdala --> </span></div></li><li><div><span style=""font-weight: 400;"">Altered gene expression in amygdala</span></div></li><li><div><span style=""font-weight: 400;"">Neurons in the amygdala began expressing more CRF....</span></div></li></ul><div><span style=""font-weight: 400;"">When CRF levels increase in Amygdala...</span></div><ul><li><div><span style=""font-weight: 400;"">More activation of magnocellular (CRF-AVP) neurons in the PVN</span></div></li><li><div><span style=""font-weight: 400;"">More cortisol released...less negative feedback</span></div></li></ul></b>"
<div>Amygdala likes to learn</div>"<b><div><span style=""font-weight: 400;"">Amygdala responsible for “emotional memories”</span></div><ul><li><div><span style=""font-weight: 400;"">Classical conditioning</span></div></li><li><div><span style=""font-weight: 400;"">Basolateral area of amygdala </span></div></li></ul><div><span style=""font-weight: 400;"">Amygdala can “learn” which stimuli or context produced elevated stress </span></div><ul><li><div><span style=""font-weight: 400;"">Associations or conditioning can be learned without conscious awareness </span></div></li></ul><div>After amygdala has “learned” what caused elevated stress → the stress response will be BIGGER the next time it happens</div><ul><li><div><span style=""font-weight: 400;"">Hyper-reactive stress response</span></div></li></ul></b>"
<div>Sensitization to Stress</div>"<b><div><span style=""font-weight: 400;"">High levels of stress can make the nervous system more responsive to future stressors</span></div><ul><li><div><span style=""font-weight: 400;"">More of a positive feedback loop than negative feedback loop</span></div></li></ul><div>Type 2 Cortisol receptors only activated by high cortisol levels</div><ul><li><div><span style=""font-weight: 400;"">Type 2 can alter gene expression → Increases release of CRF with vasopressin</span></div></li><li><div><span style=""font-weight: 400;"">Increased CRF in amygdala → more ACTH and Cortisol release (</span>increased stress reactivity<span style=""font-weight: 400;"">)</span></div></li><li><div><b><span style=""font-weight: 400;"">Increased CRF in locus coeruleus → increased arousal and alertness (</span>hypervigilance)</b></div></li></ul></b>"
<div>Long-term Effects of Stress Sensitization</div>"<b><div><span style=""font-weight: 400;"">Sensitization of amygdala</span></div><ul><li><div><span style=""font-weight: 400;"">Increased CRF expression in amygdala</span></div></li><li><div><span style=""font-weight: 400;"">Enhanced fear responses, increased HPA activity </span></div></li></ul><div><span style=""font-weight: 400;"">Increased CRF expression in central feedback system</span></div><ul><li><div><span style=""font-weight: 400;"">Increased arousal and alertness (via norepinephrine)</span></div></li></ul><div><span style=""font-weight: 400;"">Greater reactivity of the HPAC</span></div><ul><li><div><span style=""font-weight: 400;"">More ACTH and Cortisol</span></div></li></ul><div><span style=""font-weight: 400;"">Greater reactivity of the HSAM</span></div><ul><li><div><span style=""font-weight: 400;"">Cortisol stimulates increased catecholamine synthesis</span></div></li><li><div><span style=""font-weight: 400;"">Cortisol increases sensitivity of adrenergic receptors</span></div></li><li><div><span style=""font-weight: 400;"">More epinephrine and norepinephrine made</span></div></li><li><div><span style=""font-weight: 400;"">Greater response to epinephrine and norepinephrine</span></div></li></ul></b>"
CRF feedback system"<b><div><span style=""font-weight: 400;"">CRF acts as neurotransmitter that’s active throughout the brain </span></div><div><span style=""font-weight: 400;"">CRF feedback system help integrate sensory information with emotional states and behavioral responses</span></div></b>"
What CRF does"<b><div><span style=""font-weight: 400;"">In HPA → release ACTH → Release cortisol </span></div><div><span style=""font-weight: 400;"">In other brain areas</span></div><ul><li><div><span style=""font-weight: 400;"">CRF → Frontal lobes (alters attention and working memory)</span></div></li><li><div><span style=""font-weight: 400;"">CRF → Amydala (emotional memory, classical conditioning)</span></div></li><li><div><span style=""font-weight: 400;"">CRF → Hippocampus (enhance long term memory) </span></div></li><li><div><span style=""font-weight: 400;"">CRF → Locus ceruleus (activate norepinephrine circuits)</span></div></li><li><div><span style=""font-weight: 400;"">CRF → Ventral Tegmental Area (VTA)  (activate dopamine circuits)</span></div></li><li><div><span style=""font-weight: 400;"">CRF → Raphe Nucleus (activate serotonin circuits)</span></div></li><li><div><span style=""font-weight: 400;"">CRF → Immune system → trigger inflammatory response</span></div></li></ul></b>"
<div>Norepinephrine arousal system </div>"<div><b><div>Locus Ceruleus</div><ul><li><div><span style=""font-weight: 400;"">Norepinephrine arousal system </span></div></li><li><div><span style=""font-weight: 400;"">Brainstem nucleus in reticular formation</span></div></li><li><div><span style=""font-weight: 400;"">Activation increases arousal, alertness</span></div></li><li><div><span style=""font-weight: 400;"">Inactive during sleep </span></div></li></ul></b></div>"
<div>CRF in the LC Increases Arousal </div>"<b><div><span style=""font-weight: 400;"">CRF in the locus ceruleus leads to norepinephrine release throughout the brain</span></div></b><b><span style=""font-weight: 400;""><img src=""7CUKJehjkUT1ZzD4rc0usz4EFDJzINL8T3fCTpAaLKZkwsG2uSABgqSm2i2lFCyjvS_PvVUeCOOOBDw1C2X3XOMQH7gfbD81R2QIa_BjBs98AOLhL7D.png""><br></span></b><b><div><span style=""font-weight: 400;"">CRF infused into locus ceruleus (LC) of rats</span></div><ul><li><div><span style=""font-weight: 400;"">CRF in the LC increased norepinephrine in cortical and subcortical area</span></div></li><li><div><span style=""font-weight: 400;"">CRF triggered state of ”high alert”</span></div></li></ul></b>"
<div>Sensitization as Adaptive</div>"<b><div><span style=""font-weight: 400;"">Sensitization allows continued stress response despite existing levels of high stress</span></div><ul><li><div><span style=""font-weight: 400;"">The stress response does not habituate </span></div></li><li><div><span style=""font-weight: 400;"">Continues to respond </span></div></li></ul><div><span style=""font-weight: 400;"">High levels of cortisol may indicate that the environment is dangerous</span></div><div><span style=""font-weight: 400;"">Sensitization increases arousal and alertness</span></div><ul><li><div><span style=""font-weight: 400;"">Hypervigilance to detect potential threats</span></div></li></ul><div><span style=""font-weight: 400;"">Greater reactivity</span></div><ul><li><div><span style=""font-weight: 400;"">As levels of stress increase, response to stress continues to increaseSensitization as Adaptive</span></div></li></ul></b>"
<div>When being sensitive becomes maladaptive</div>"<b><div><span style=""font-weight: 400;"">In a dangerous environment, greater vigilance and stress reactivity is adaptive</span></div><ul><li><div><span style=""font-weight: 400;"">In a warzone, need to be vigilant to possible threats</span></div></li></ul><div><span style=""font-weight: 400;"">But... the sensitization may no longer be adaptive in a safe environment</span></div><ul><li><div><span style=""font-weight: 400;"">The sensitization is long-lasting (and can be self-reinforcing)</span></div></li><li><div><span style=""font-weight: 400;"">Hypervigilance → Emotional appraisals of threats</span></div></li><li><div><span style=""font-weight: 400;"">Increased stress reactivity → </span><span style=""font-weight: 400; text-decoration-line: underline;"">more hypervigilance</span></div></li><li><div><span style=""font-weight: 400;"">Physiological damage = </span>Allostatic loa<span style=""font-weight: 400;"">d</span></div></li></ul><ul><li><div><span style=""font-weight: 400;"">Psychological and Social damage</span></div></li></ul><div><span style=""font-weight: 400;"">-Anxiety, irritability, social withdrawal When being sensitive becomes maladaptive</span></div></b><br>"
<div>Vulnerable to being Sensitive</div>"<b><div><span style=""font-weight: 400;"">Individual differences in stress sensitization </span></div><ul><li><div><span style=""font-weight: 400;"">Those with a smaller hippocampus may be more vulnerable to stress sensitization </span></div></li></ul><div>Role of the hippocampus<span style=""font-weight: 400;""> </span></div><ul><li><div><span style=""font-weight: 400;"">Hippocampus stimulates the production of cortisol (under normal cycle)</span></div></li><li><div><span style=""font-weight: 400;"">But also inhibits HPA axis when cortisol levels are high</span></div></li><li><div><span style=""font-weight: 400;"">Individual with smaller hippocampus, more trouble regulating daily cortisol</span></div></li></ul><div><span style=""font-weight: 400;"">Decreased volume of hippocampus is a risk factor for PTSD</span></div><ul><li><div><span style=""font-weight: 400;"">Hypervigilance and reactivity common symptoms of anxiety</span></div></li></ul></b>"
<div>Stress and Long-Term Memory</div>"<b><div><span style=""font-weight: 400;"">Memories of traumatic, stressful, or emotional events</span></div><ul><li><div><span style=""font-weight: 400;"">More vivid and detailed than non-emotional memories</span></div></li></ul><div><span style=""font-weight: 400;"">Feedback mechanisms of stress hormones influence functioning of the amygdala and hippocampus </span></div><ul><li><div><span style=""font-weight: 400;"">Cortisol has direct feedback effects on amygdala and hippocampus</span></div></li><ul><li><div><span style=""font-weight: 400;"">Type 2 cortisol receptors in amygdala</span></div></li><li><div><span style=""font-weight: 400;"">Cortisol negative feedback with hippocampus (decreases HPAC activity)</span></div></li></ul><li><div><span style=""font-weight: 400;"">Epinephrine indirect feedback mechanism through vagus nerve</span></div></li><ul><li><div><span style=""font-weight: 400;"">Epinephrine in blood can’t pass through blood-brain barrier</span></div></li><li><div><span style=""font-weight: 400;"">Beta-adrenergic receptors on vagus nerve → increase activity of basolateral amygdala</span></div></li><li><div><span style=""font-weight: 400;"">Activation of the amygdala → activation of hippocampus </span></div></li></ul></ul><div><span style=""font-weight: 400;"">Increased activation of amygdala and hippocampus promotes memory consolidation</span></div></b><br>"
Memory Consolidation"<b><div><span style=""font-weight: 400;"">the process of making memories more long-term </span></div><ul><li><div><span style=""font-weight: 400;"">Emotional memories more likely to be consolidated</span></div></li><li><div><span style=""font-weight: 400;"">Connections between amygdala and hippocampus</span></div></li></ul><div><span style=""font-weight: 400;"">Experimental administration of cortisol enhances memory for emotional stimuli</span></div><ul><li><div><span style=""font-weight: 400;"">Both positive and negative stimuli</span></div></li></ul><br><div><span style=""font-weight: 400;"">High levels of cortisol generally impair long-term memory...but can enhance memory for emotional information</span></div><ul><li><div><span style=""font-weight: 400;"">Like enhanced memory for details of traumatic events </span></div></li></ul></b>"
<div>Stress and Working Memory </div>"<b><div><span style=""font-weight: 400;"">Cortisol also has impacts on working memory</span></div><ul><li><div><span style=""font-weight: 400;"">Requires executive functions of the frontal lobes</span></div></li><li><div><span style=""font-weight: 400;"">Ability to concentrate and regulate attention </span></div></li></ul><br><div><span style=""font-weight: 400;"">Fronto-limbic connections between amygdala and frontal lobes</span></div><br><div><span style=""font-weight: 400;"">Experiments demonstrate that production of high cortisol levels in response to stressors impaired attentional control </span></div><ul><li><div><span style=""font-weight: 400;"">Less able to direct attention during dichotic listening task </span></div></li></ul><br><div><span style=""font-weight: 400;"">High levels of cortisol impair working memory =  Poor ability to regulate attention</span></div></b><br>"
<div>Prolonged Consequences of Prolonged Stress</div>"<b><div><span style=""font-weight: 400;"">An intense or prolonged stress will </span>activate both HSAM and HPA<span style=""font-weight: 400;"">C</span></div><ul><li><div><span style=""font-weight: 400;"">Activation of both makes the sympathetic response bigger and allows cortisol levels to increase to high levels</span></div></li></ul><br><div><span style=""font-weight: 400;"">The stress response can become sensitized</span></div><ul><li><div><span style=""font-weight: 400;"">Activation of Type 2 receptors in the amygdala</span></div></li><li><div><span style=""font-weight: 400;"">Amygdala “learns”  </span></div></li><li><div><span style=""font-weight: 400;"">Increases activation of the CRF feedback system</span></div></li></ul><br><div><span style=""font-weight: 400;"">Psychological/Physiological effects</span></div><ul><li><div><span style=""font-weight: 400;"">Become hypervigilant (looking for threats)</span></div></li><li><div><span style=""font-weight: 400;"">Less attentional control (unable to redirect focus of attention)</span></div></li><li><div><span style=""font-weight: 400;"">Heighten memory for emotional stimuli</span></div></li><li><div><span style=""font-weight: 400;"">Allostatic load  (increased inflammation, impaired immune function</span></div></li></ul></b>"
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