Transcript Emotions and Limbic System

Fear, Anxiety Disorders and
Amygdala
PSY391S
March 29, 2006
John Yeomans
Limbic System Anatomy
• Oldest areas of telencephalon, bordering
diencephalon. Limbic means "border".
• Connections with olfactory and taste
systems, hypothalamus (visceral &
emotional).
• Transition from subcortex (e.g. amygdala)
to 3-4 layered cortex (e.g. hippocampus)
to 6-layered neocortex.
• Interconnections--"Papez Circuit"
• Unconditioned fear mediated through
PAG.
Amygdala and Conditioned Fear
Extended Amygdala and Emotions
• Subcortical parts of limbic system.
• Amygdala, BNST, Basal Forebrain
(olfactory tubercle, Ventral pallidum,
septum and basal n.), n. accumbens.
• Fear and emotion learning (amygdala),
sex and maternal behavior (medial
amygdala, BNST, ventral pallidum), and
reward learning (n. accumbens).
Monogamous voles have more
Vasopressin in their Ventral
Pallidum.
Young et al.
Bed Nucleus and Gender Identity
• Central n. of BNST is sexually dimorphic in
humans—larger in males by 44%.
• 6 transgendered males had smaller
BNSTc.
• Not related to partner preference.
• No differences in MPO areas that are
sexually dimorphic.
• Correlation, not causal link.
Early Studies
• Temporal lobe lesions (Klüver-Bucy
Syndrome) lead to tame monkeys,
fearless and hypersexual.
• Temporal lobe epilepsy leads to emotional
auras and behaviors.
• Stimulation of amygdala leads to attack,
rage or positive affect.
• Stimulation of hippocampal region leads to
experiential reports "deja vu".
CS Tone, US shock
LeDoux, Davis
Deep superior
colliculus
Startle
Fear Potentiation
Fear Learning
• Unlearned emotional responses activated
through PAG (central gray), SC, BNST and
hypothalamus.
• Associations between CS and US occur in
lateral and basolateral n.
• Fast CS auditory path via thalamus, slow
CS path via auditory cortex.
• Context associations via hippocampus.
/Deep SC
Pharmacology of Fear and Anxiety
• Fear inhibited by benzodiazepines (GABAA
agonists) in amygdala. Fear activated by
glutamate.
• Panic activated by CCKB in amygdala.
• Stress/anxiety activated by CRH in BNST.
• Peripheral effects of stress hormones
(CRHACTHcortisol) and central
effects on limbic system.
Anxiety Disorders I
• Phobias: Specific fears, often learned. Treated
by psychotherapy “progressive desensitization”.
• Panic attacks: Severe sympathetic overreactions
to uncomfortable situations. Usually treated with
tranquillizers and psychotherapy. Amygdala?
• Post-traumatic stress: Fear brought on by specific
trauma, e.g., violence or accident. Nightmares.
• Generalized anxiety: Persistent excessive worries,
associated with depression. Treated with SSRIs or
tranquillizers.
Posttraumatic Stress Disorder
Anxiety Disorders II
• Obsessive-compulsive disorders:
Uncontrollable and irrational desire to
perform repetitive tasks, e.g. washing, or
checking for safety. Overactivity in
striatum. Treated with neuroleptics.
• Tourette’s Syndrome: Uncontrollable tics,
either motor or verbal. Treated with
neuroleptics.
Frontal Cortex and Emotions
• Orbital, medial prefrontal and cingulate.
• Conscious processing of rewards and
punishers.
• Important in depression (fMRI) and SSRI
antidepressant actions.
• Long-term planning of emotions, motives
and actions.
• Weak lateralization of emotions in right
frontal cortex.
Areas Changed by Emotions
(fMRI)
Yellow--Orbitofrontal
Blue--Anterior Cingulate
Green--Posterior Cingulate
Purple--Insula
Red--Amygdala
Depression
• Irrational feelings of failure and hopelessness,
loss of appetites, loss of energy, sleep disorders.
• Treated with selective serotonin reuptake
inhibitors, benzodiazepines, and/or cognitive
psychotherapy.
• SSRIs take weeks to work, perhaps due to
stimulation of neurogenesis in hippocampus.
• Often associated with generalized anxiety, and
can be treated with tranquilizers short term.
Brain Changes
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Increased activity in amygdala, mediodorsal
thalamus, medial orbitofrontal cortex.
Benzodiazepines inhibit amygdala and many
other areas.
SSRIs inhibit orbitofrontal cortex. Also, activate
hypothalamus feeding/energy system for
weight loss.
Cognitive therapy inhibits anterior cingulate.
Electroconvulsive shock still used occasionally,
e.g. suicide, poor drug effect. Cingulotomy less
often (pain and depression).
Cingulate and Depression
• Cingulotomy (cutting fibers of anterior
cingulate) relieves persistent pain and
depression.
• Stimulation of subgenual anterior cingulate
(Area 25) relieves persistent depression in
a few treatment-resistant people.
Bipolar Disorder
• Manic-depression (now called “bipolar disorder”)
results in severe mood swings from high to low.
• Usually cyclic, with shorter highs of great energy,
self-confidence and destructive behaviors
(spending, gambling, escapades), followed by
longer periods of depression.
• Treated with lithium, which effectively smooths
out highs and lows, but mechanism still
unknown.
• Widespread brain changes.
Schizophrenia
• Positive symptoms: hallucination and delusions.
Loss of contact with reality.
• Negative symptoms: social withdrawal, poor
grooming.
• Cognitive symptoms: poor intellectual
functioning.
• Positive symptoms treated by D2 blockers
(typical neuroleptics).
• Negative symptoms also treated with atypical
neuroleptics (e.g. clozapine) but mechanism still
unknown.
Brain Changes
• Dopamine system or receptors? Amphetamine
psychosis.
• Phencyclidine (PCP) psychosis suggests that
NMDA inhibition also important.
• Low frontal cortex activity.
• Changes in hippocampus organization.
• Reduction in cortical mass, and hippocampal/
amygdala mass, with enlargement of ventricles.
• Causes? Strongly genetic, but many genes.
Environment—Drug taking, prenatal viruses
(cytokines slow brain development in
pregnancy?)
Male vs. Females
• More females than males have depression
and some anxiety disorders.
• More males have schizophrenia, with
earlier onset and greater severity.
• Estrogens may be protective factor,
because some women get schizophrenia
at menopause.