HYPOTHALAMUS

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HYPOTHALAMUS LIMBIC SYSTEM
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EMOTION

• Emotion has been a notoriously difficult concept
  to define. Many psychologists argue that an
  emotion comprises three different elements
• cognitive (thinking) component an appraisal or
  judgment  
• feeling (subjective) component what a person
  experiences privately  
• action (or, action tendency) component either an
  action or, at least, a tendency to an action

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Consciousness Emotions

• Absence Seizures a type of epilepsy in which for
  a period of time (usually lt 30 seconds) an
  individual stares blankly silently and, then,
  begins to move without any sense of purpose.
  Afterwards there is no recollection of the
  experience and no sense of emotion. The absence
  of either emotional display during the seizure or
  recollection afterwards argues for the need of
  consciousness in order to feel emotion.
•  

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Emotion vs. DecisionWhat Would You Do?
You see a runaway trolley car rushing down the
tracks and know that the trolley will kill five
people walking along the tracks who don't
realize it is headed their way. There is a
switch in front of you which would immediately
divert the trolley to a different set of tracks.
However, there is a man walking on those tracks
who would be killed if you threw the switch.
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Emotion vs. DecisionWhat Would You Do?
From a footbridge above the tracks, you see a
runaway trolley car rushing toward five people
walking along the tracks who don't realize it is
headed their way. They will be killed if the
trolley doesn't stop. But, there is a man near
you on the bridge. If you push him off the
bridge, he will topple onto the tracks, be
killed, but stop the trolley. You have to decide
whether to push him and save the five people or
not push him and watch them die.
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Emotions Decisions
when we make decisions, we activate different
brain areas if the decision is laden with
emotion. The areas associated with increased
emotionality include Cingulate gyrus Angular
gyrus Medial frontal gyrus
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Are "gut" feelings a good basis for a
decision?Pres. Bush says they are. But, what
about evidence?

• Snake/Spider Reaction Study (Katkin, Wiens,
  Öhlman, 2001)
• View slides of snakes or spiders for 10
  milliseconds and try to guess which was seen?
• If body is given slight shock, the heart rate
  would increase.
• Eventually, participants could actually guess
  correctly by paying attention to their heart rate
  alone.
• Thus, if you are good at detecting your autonomic
  nervous system responses, you may have valid
  reactions about dangers you can't consciously
  detect.

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Brain Damage, Emotion, Decisions

• Iindividuals with brain damage that affects their
  emotions make very poor decisions.
• Case 1 Man with prefrontal cortex damage no
  emotions felt he got neither pleasure nor pain
  from anything.
• He knew what the outcomes would be for different
  actions. But, he could not choose which to do
  because it was not clear to him whether he
  preferred a "good" or a "bad" outcome. 
• Case 2 Young adults who suffered injury to
  prefrontal cortex in infancy.
• Never learned moral behavior stole, lied, abused
  others, etc. No guilt.
• No friends and could not hold jobs.
• This reminds me of the studies of Dr. Dorothy
  Otnow Lewis among juveniles and adults sentenced
  to death for murder (Lewis, 1998, 2004). She
  consistently found histories of significant brain
  trauma in such convicts.
•  

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Arousal Emotions

• Is ANS arousal necessary for emotions?
• People can categorize situations (that is, have a
  cognitive reaction) which elicit happiness or
  anger without experiencing any glandular or
  muscular changes. However,
• Feelings (subjective experiences) are absent or
  minimal without ANS arousal.

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ANS Arousal

• Pure Autonomic Failure (PAF) A rare condition of
  middle- and late-adulthood in which ANS output to
  the body fails, e.g., individual stands up
  without ANS compensating for the effect of
  gravity. Such individuals tend to faint. Patients
  with PAF report emotions, but they experience
  them as very weak or mild.  

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ANS Arousal

• Locked-In Syndrome Patients with damage to the
  ventral brainstem are completely paralyzed, that
  is, unable to move any of their body (except for
  their eyes) although they are completely alert.
  They can be trained to communicate using those
  eye movements. Most people with locked-in
  syndrome report feeling tranquil (not terrified
  or suicidal or depressed). Without receiving any
  ANS input, the individual's brain only receives
  messages suggesting tranquility.

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ANS Arousal

• Is ANS arousal sufficient for emotions?
• Mild emotional differences or feelings Do not
  appear to be related to a person's reading of
  mild differences in the state of the ANS.
• Extreme Arousal
• Panic Disorder Extreme sympathetic system
  arousal (increased heart rate, increased
  breathing similar to experience of suffocating)
  which is interpreted as fear

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Effects of Facial Expressionon Emotions
Individuals who adopt the physical postures
associated with some emotions, e.g., smiling or
frowning, report that they experience the same
stimuli in different ways, e.g., if forced to
smile (clenching a pen in the teeth), people find
comic strips funnier than if they are forced to
remain closed-mouthed (holding a pen between the
lips).
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Limbic System Functions
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Limbic System Functions

•  RH more sensitive to emotional stimuli than the
  left hemisphere (LH). For example,
• Right amygdala activated by laughing or crying
• Right temporal cortex scanning faces for
  emotional expression increases activity
• RH damage Difficulty interpreting facial
  expression indicating viewing pleasant or
  unpleasant scene
• LH damage Higher than normal ability to
  interpret facial expression greater than even
  chance to detect lying (60 vs. 50)
• RH inactivation facts, but not strong emotions,
  of past events remembered
• RH gt LH activity associated with shyness
• LH gt RH activity associated with outgoing
  fun-loving personality

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Central ANS regulation Amygdyla projects to
thalamus - relay to cortex (cognition) and
hypothalamus (ANS, survival)
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Thalamus relay to cortex for cognition and
executive decision
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Limbic hypothalamic connectivity
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NA - DA, reward, pleasure LC - NE, ANS,
visceral responses
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VMHN stimulation satiety lesion hyperphagia
(overeating)
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Physiology of Satiety
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LHN stimulation feeding lesions anorexia
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Physiology of Hunger
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Monoamine pathways project thru MFB
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LC Source of noradrenergic (NA) connectivity
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LC stimulation increases NE in ventral brainstem
CVR and RESP Centers and throughout cortex
NE injected into anterior temporal lobe
structures also initiates feeding behavior.
Therefore, adrenergic processes in the cortex,
limbic system, and hypothalamus regulate feeding.
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NA and SN sources of DA for movement and reward
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ICSS produces spontaneous verbal reports of
pleasure. The type of pleasurable sensation
depends on the stimulation site. Responses
reflect feelings of motivational systems,
including sex, hunger, thirst, the need for
sleep, defecation, rest, etc.
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MRN source of 5-HT regulates release of DA in
NA and of Enk in hypothalamus controls pleasure
and anti-nociception
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5-HT projections via reticulospinal tracts to
SC Stimulates release of Enk in SC for
anti-nociception
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Lesions and electrical stimulation of
hypothalamic and limbic system sites alter the
expression of rage, anger and the behavioral
complex of social dominance.
Tumors of amygdyla known to produce
uncontrollable rage
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Pontine and hypothalamic mediation of anger

• After all brain tissue above the pons is removed,
  cats and dogs growl, spit, scratch, and bite when
  handled roughly. When decerebrated above the
  hypothalamus, animals have a subnormal threshold
  for rage they become violent at the slightest
  touch, and their attacks are much better
  integrated. Such attacks include running, biting,
  and well-timed and well-aimed clawing. Therefore,
  the mesencephalon contains motor circuits for
  attack that may be fired by strong sensory input
  from the body or by input from hypothalamic
  mechanisms that amplify and organize sensory
  input. However, normal animals do not respond
  with rage to every tactual stimulus, and
  domesticated animals will tolerate rough
  handling. Normally, the expression of anger is
  suppressed by higher cortical structures until an
  appropriate time for release arises.

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Dave - large dominant male feared by all other
monkeys but Riva active, aggressive.
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(Deep) Temporal Lobe Lesions

• Following lesions of Riva's amydala, there were
  no other animals striving for dominance in the
  troupe. The interest of the three adolescents
  remained focused on their subgroup, while the
  others cowered and submitted. In that situation,
  the effects of amygdalectomy were opposite to the
  effects observed when an animal was challenged by
  active competitors.
• This has important implications for the
  understanding of human temporal lobe dysfunction.
  Humans differ from birth and operate in varied
  social context. While it is clear that mood and
  dominance change following temporal lobe lesions,
  it is difficult to predict the direction of
  change.

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The Pleasure (Reward) Center

• The nucleus accumbens is the engine of the reward
  response. And, in recent studies researchers
  determined that the reward pathway activates pain
  relief through the release of both opioids, a
  morphine-like drug produced by the body, and
  dopamine, a chemical messenger whose effects can
  be mimicked by amphetamine and cocaine, in this
  structure. The finding overturns the long-held
  assumption that the release of dopamine in the
  nucleus accumbens is associated only with
  positive experiences.
• Nociceptive (pain) stimuli depress mood and
  increase anxiety, irritability
• Antinociceptive (pain relief, analgesic)
  mechanisms elevate mood and decrease anxiety,
  irritability

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Start (Approach, Repeat Behavior), Stop Signals,
Pain and Pleasure

• The reward pathway is a neural network in the
  middle of the brain that prompts good feelings in
  response to certain behaviors, such as relieving
  hunger, quenching thirst or having sex, and it
  thereby reinforces these evolutionarily important
  drives. However, the circuit also responds to
  drugs of abuse, such as heroin, cocaine,
  amphetamine and nicotine, which seem to hijack
  the circuitry, altering the behavior of its
  neurons.

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Addiction Disorders and Naloxone

• The evolutionary value of a rush of analgesia is
  clear, as it could allow, for example, a badly
  injured individual to escape an attacker. It
  probably could also explain why some individuals
  can be injured without persistent pain.
• But the phenomenon may also explain why heroin
  addicts, in withdrawal, can experience pain or
  increased sensitivity to painful stimuli. It may
  be that one of the reasons people stay addicted
  is to avoid going through this unpleasant state
  of withdrawal.
• Under other conditions, it's possible that a
  painful stimulus, by activating the nucleus
  accumbens, might itself be experienced as
  rewarding, as appears to occur in self-injurious
  behaviors. Interestingly, treatment for this
  class of disorders, characterized by pursuit of
  painful experiences often for apparent
  thrill-seeking value, includes administration of
  naloxone, a drug that blocks the effects of
  opioids in this reward circuit.
• Naloxone (Narcan) is the antidote for narcotic
  drug overdosages

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Role of SN and DA

• GABA and DA in nigrostriatal system modulates DA
  in nucleus accumbens elevating mood and
  stimulating start, approach, repeat behavior
  signals
• Addictive drugs and behaviors increase DA in NA
• Acupuncture, orgasm and physiological reward
  response increases DA
• DA receptors in limbic system (e.g., amygdyla and
  septal nuclei for reward of sex behaviors)
  stimulated
• DA stimulates release of serotonin
• DA receptors in prefrontal cortex involved in
  executive decisions (start vs. stop, right vs.
  wrong)
• DA-2 receptor deficiency involved in autism,
  schizophrenia, addictive disorders,
  post-traumatic stress disorder, bipolar disease
  suggesting a Reward Deficiency Syndrome may be
  a common genetic mechanism for these disorders
• The D2 A1 allele is an abnormal D-2 receptor that
  makes individuals susceptible to these disorders)
  

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Reward and Self-Stimulation

• Self-stimulation behaviors studied as a paradigm
  for reward, elevation of mood and antinociception
  in animals but controversial in humans because of
  free will
• Drugs and behaviors that increase
  self-stimulation increase pain threshold
• Drugs and behaviors that decrease
  self-stimulation decrease pain threshold

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DA anti-stress molecule

• The dopaminergic system, and in particular the
  dopamine D2 receptor, has been implicated in
  reward mechanisms. The net effect of
  neurotransmitter interaction at the mesolimbic
  brain region induces "reward" when dopamine (DA)
  is released from the neuron at the nucleus
  accumbens and interacts with a dopamine D2
  receptor. "The reward cascade" involves the
  release of serotonin, which in turn at the
  hypothalmus stimulates enkephalin, which in turn
  inhibits GABA at the substania nigra, which in
  turn fine tunes the amount of DA released at the
  nucleus accumbens or "reward site." It is well
  known that under normal conditions in the reward
  site DA works to maintain our normal drives. In
  fact, DA has become to be known as the "pleasure
  molecule" and/or the "antistress molecule."

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Stress response Release of CRH by hypothalamus
and ACTH by pituitary and release of cortisol by
adrenal cortex and of epinephrine from adrenal
medulla (sympathetic mediator)
Nociceptive inputs stimulate stress response and
anti-nociceptive inputs block stress response
(anti-stress)
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Reward Deficiency Syndrome

• When DA is released into the synapse, it
  stimulates a number a DA receptors (D1-D5) which
  results in increased feelings of well-being and
  stress reduction. A consensus of the literature
  suggests that when there is a dysfunction in the
  brain reward cascade, which could be caused by
  certain genetic variants (polygenic), especially
  in the DA system causing a hypodopaminergic
  trait, the brain of that person requires a DA fix
  to feel good. This trait leads to multiple
  drug-seeking behavior. This is so because
  alcohol, cocaine, heroin, marijuana, nicotine,
  and glucose all cause activation and neuronal
  release of brain DA, which could heal the
  abnormal cravings. Certainly after ten years of
  study we could say with confidence that carriers
  of the DAD2 receptor A1 allele have compromised
  D2 receptors. Therefore lack of D2 receptors
  causes individuals to have a high risk for
  multiple addictive, impulsive and compulsive
  behavioral propensities, such as severe
  alcoholism, cocaine, heroin, marijuana and
  nicotine use, glucose bingeing, pathological
  gambling, sex addiction, ADHD, Tourette's
  Syndrome, autism, chronic violence, posttraumatic
  stress disorder, schizoid/avoidant cluster,
  conduct disorder and antisocial behavior. In
  order to explain the breakdown of the reward
  cascade due to both multiple genes and
  environmental stimuli (pleiotropism) and
  resultant aberrant behaviors, Blum united this
  hypodopaminergic trait under the rubric of a
  reward deficiency syndrome.

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Depression

• Catecholamine Imbalance. The concept of a Reward
  Deficiency Syndrome provides a working model for
  studying the mechanism by which antidepressant
  drugs accomplish their therapeutic effect. Some
  antidepressants (e.g., monoamine oxidase
  inhibitors (MAOI and imipramine), are known to
  elevate brain levels of catecholamines. One side
  effect of L-Dopa (a precursor of dopamine used to
  treat akinesia in Parkinson's Disease) is that it
  sometimes leads to excessive emotional behavior
  while drugs that lower brain catecholamine levels
  commonly produce depression as a side effect
  (e.g., reserpine and tetrabenazine, which treat
  hypertension). This suggests that one factor in
  depression could be a reduction in available
  catecholamines adversely affecting the activity
  of dopaminergic neurons in the reward system.
• Serotonin. Fluoxetine (e.g., Prozac) is a
  successful antidepressant that is an SSRI and has
  no cholinergic, adrenergic, or histaminergic
  receptor blocking properties. The effect of SSRI
  compounds involves more than blocking re-uptake
  of the serotonin into the presynaptic vessicle.
  These drugs may alter the normal metabolic
  sequence of serotonin and alter concentration s
  of psychoactive metabolites of serotonin.
  Serotoninergic neurons are involved in the
  response to stress. It appears that dysregulation
  of the body's response to stress is an important
  component of many cases of depression.
• Hormones. The stress system of the brain is a
  complex of neuronal, hormonal, and immunological
  responses. It comes into play when a stress
  provokes the brain, causing its hypothalamic
  centers to release corticotropin-releasing
  hormone (CRH). In turn, CRH stimulates the
  pituitary gland and finally the adrenal glands
  that release cortisol. Cortisol constitutes the
  main circulating steroid associated with stress
  in humans. Many depressed patients show
  chronically elevated blood cortisol, implying a
  malfunction in the system that ordinarily
  controls cortisol. When excess cortisol reaches
  its receptor in the hippocampus and other limbic
  sites, CRH production is reduced however,
  production of CRH is excessive in depressed
  patients, and the suppression fails.
• Brain injury per se engenders increased
  probability of depression. Part of this involves
  secondary response to the patient's recognition
  of future disability.

Shortcut to ovation
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Lewis Carroll, Alices Adventures in Wonderland

• Alice, speaking to the Cheshire Cat
• Would you tell me, please, which way I ought to
  go from here?
• That depends a good deal on where you want to
  get to, said the Cat.
• I dont much care where, said Alice.
• Then it doesnt matter which way you go, said
  the Cat.
• so long as I get somewhere, Alice added as an
  explanation.
• Oh, youre sure to do that, said the Cat, if
  you only walk long enough.

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