Neuro: Fear, Anxiety, and Stress

Cued Fear Learning (classical conditioning)

Conditioned stimulus (CS) signals aversive (painful) unconditioned stimulus (US). So presentation of CS can produce a conditioned fear response (CR). Ex. Sound = CS and shock = US

What does fear learning depend upon?

Amygdala especially outputs from the CENTRAL AMYGDALA

What does threatening stimuli activate?

Basolateral amygdala that then in turn activates the central amygdala.

What does activity of neurons in the central amygdala generate?

A fear response in activating fear circuitry responsible for:

• freezing of limb movements

• sympathetic nervous system activation

• increased vigilance

Outputs here give rise to fear (threat) response

Before the pairing

Tone is a neutral stimulus and does not produce fear.

After pairing

Tone is a conditioned stimulus and now produces fear.

What happens when the amygdala is damaged?

No signs of fear and can’t recall experiences of fear and can’t recognize facial expressions of fear.

What temporal alignment is in classical conditioning?

Delay conditioning is most robust. AKA overlap of CS with US but CS plays first.

Fear Extinction

Does not erase fear memory, rather forms new competing memory that is SAFE. Fear response can decrease. If CS is presented many times in absence of US, the fear response to CS diminishes. However, that does not mean it can’t come again.

Spontaneous recovery

even if fear is extinguished, presentation of CS a week later can still produce a fear response so original CS-US fear association was not lost. new additional association, CS-No US aka new (safe) association.

What is the ventromedial prefrontal cortex (vmPFC) critical for?

Extinction learning and recall, and to reduce the fear response

Acquisition of Cued-Fear across age

children, adolescents, and adults can all equally learn fear association

What happens to adolescence in cued-fear extinction?

there is less than in preadolescent and adult.

What about fear extinction in childhood?

It is high, this suggests their memory is less stable. Also less spontaneous recovery of fear.

Is preadolescent “fear extinction” due to simple degradation/decay of the fear memory?

NO! Preadolescent “fear extinction” is not due to simple decay of memory (tone=shock) but instead due to greater susceptibility to interference from competing association (tone = no shock)

Cued Fear

With conditioned stimulus aka tone

Contextual fear

In the room of the place you got shocked but conditioned stimulus not played

Hippocampus is important in what in fear?

Very important in contextual fear learning

What happens to adults and children for freezing response in contextual fear?

High freezing in both.

What happens to adolescents for freezing response in contextual fear?

show no contextual fear because their fear response was suppressed. if they grow to be adults, they will show the fear response. (ex. shocking adolescent mice in a cage and putting them back in the cage as adults and they freeze)

Anxiety disorders

characterized by excessive fear and anxiety in absence of threat

• Posttraumatic stress disorder (PTSD)

• Social anxiety disorder

• Specific phobias

• Generalized anxiety disorder

Posttraumatic stress disorder (PTSD)

intense fear is triggered by reminders of a traumatic event, often one that involved threat of death or serious injury.

Social anxiety disorder

Intense fear of social embarrassment and MOST COMMON.

embarrassment in social situations.

• DIFFERENT FROM Agoraphobia: avoid crowded or other places that cause panic. avoidant of situations and panic in crowded places (ex. BJ Casey’s son avoiding social situations)

Specific phobias

Anxiety is triggered by specific objects or situations. (ex. spiders, cats, etc.)

Generalized Anxiety Disorder

Persistent and excessive worry. In situations where there is little cause for concern. People with this expect the worse

What happens when individuals with social anxiety, specific phobias, and generalized anxiety disorder are shown photographs with negative emotional content?

High reactivity of the amygdala relative to controls.

What happens when individuals with PTSD are shown photographs with negative emotional content?

Show reduced responsivity of ventromedial prefrontal cortex.

Psychological therapies

Can reduce excessive anxiety.

Psychological therapies: systematic desensitization/exposure therapy

client relaxed when exposed to stimuli that resemble that anxiety and with successive presentation it reduces anxiety

Psychological therapies: Cognitive Behavioral Therapy

client learns to challenge and reevaluate their anxiety-related thoughts processes (can include exposure too)

Drug therapies

can reduce anxiety

Drug therapies: Selective serotonin reuptake inhibitors (SSRIs)

Such as prozac that elevate synaptic serotonin levels

Drug therapies: Benzodiazepines

Such as Xanax that reduces anxiety by increasing effects of inhibitory neurotransmitter GABA

What shows best efficacy when treating excessive anxiety?

Combination of drug and psychological therapies.

How do adolescents respond to exposure therapy?

Less response than adults and children. Children are not reliant on prefrontal cortex. vmPFC-amygdala circuitry and function changes with age

Memories are?

Dynamic and malleable.

Memory reconsolidation

Previously consolidated memories being recalled and actively consolidated. Maintains, strengthens, and modify memories already stored in long-term memory.

Temporal dynamics are key

sweet spot of protein synthesis when memory is consolidated to update memory

Reminder Cue then Extinction

Changes memory to erase the fear and also works in adolescents with developing vmPFC

What are the effects of combining opposing behaviors (cued and contextual fear learning)?

Fear decreases more.

What development changes in the brain may help explain these behavioral effects? PFC?

Involved in both fear expression (PL) and extinction (IL). Fear expression maintain fear (PL to BLA to CEA). Fear extinction inhibits fear (IL to ITC/inhibitory cells to CEA).

How is the hippocampus involved in contextual fear?

It plays an important role in fear expression and fear extinction by modulating the activity.

How are projections into PFC changing during adolescence?

Increased projections to prelimbic cortex (PL) from amygdala and hippocampus. Surge in amygdala projections to PL may explain sustained cued fear (diminished cued fear extinction) while surge in hippocampus projections to PL explain lack of contextual fear,

Stress

Any type of changed that we experience that causes physical, emotional, or psychological strain. It is your body’s response to anything that requires attention or action. May be mild, intense, acute, or chronic.

Hypothalamic-pituitary-adrenal (HPA) axis

Hypothalamus, pituitary and adrenal gland make up this and together they control and release the body’s key stress hormones and released from adrenal glands.

What happens when the brain interprets an environmental event as a stressor?

Corticotropin-releasing hormone (CRH) is released from hypothalamus. This triggers released of adrenocorticotropic hormone (ACTH) from the anterior pituitary. Then results in release of glucocorticoid stress hormones from the adrenal cortex. This HPA response is delayed and longer lasting than the fight and flight of the sympathetic nervous system.

How do you reduce the activity of the HPA axis and limit glucocorticoid release aka negative feedback?

Glucocorticoids pass the blood-brain barrier and nearly all brain areas containing glucocorticoid receptors. High glucocorticoid levels cause hypothalamus to release less CRH and cause the pituitary to release less ACTH. This leads to reduced glucocorticoid release from adrenal cortex.

What happens when experimental animals lack glucocorticoid receptors in the brain?

They act fearless when placed in stressful conditions.

What happens when experimental animals are genetically modified to lack glucocorticoid receptors in the brain?

They also show less stress and fear in stressful conditions.

What are glucocorticoids produces brain changes related to?

Increased amygdala activity and reduced prefrontal and hippocampal activity.

Amygdala in stress

Increased neuronal excitability, dendritic branches, dendritic spines

Hippocampus in stress

Opposite of Amygdala

Decreased neuronal excitability and number of dendrites

Prefrontal cortex in stress

Decreased neuronal excitability and number of dendrites

What happens when the brain detects threatening stimuli?

It activates the sympathetic nervous system and the HPA axis.

What is the key control center for the sympathetic nervous system stress response?

Within the medulla

What about the amygdala and other threat-detecting brain areas? How do they respond to threatening situations?

Communicate with neurons in the brainstem to modulate sympathetic nervous system response to perceived threats. They also activate the hypothalamic pituitary-adrenal (HPA) axis.

Allostatic Load

“wear and tear” on the body with repeated responses to stressful situations both internal and external

Chronic Stress

Worsens medical conditions in the brain and body (depression, cardiovascular and neurodegenerative diseases, and cancer. Inflammation is common pathways of stress-related diseases.

Stability

One’s ability to maintain homeostasis. If good, less response to stressful situations both.

Resilience

ability to return to the balance state quickly even if individual has a big response to stressful.

What makes a person resilient to stress?

Social support, individual’s perspective (aka positive and negative life experiences), feelings of gratitude, exercise, meditation, yoga

How does early life experiences relate to stress responses?

It can produce long-lasting changes in stress responses. (nature vs. nurture)