PSYC 3852: Neurobiology of Stress - Quiz 1

Learned Helplessness

A phenomenon where an individual, after experiencing repeated, uncontrollable stress/stressful situations, stops trying to change their circumstances, even when opportunities for change are available.

Used in psychology/neuroscience as a model to understand:

• Depression

• Stress-coping

• Perceived control

• Prefrontal cortex regulation of stress response

Seligman & Maier

Scientists that conducted experiments that discovered learned helplessness;

Original experiments involved dogs and how perceived control affects stress response

Used a triadic yoked design

Triadic yoked design

A specialized, three-group experimental design widely used in psychology and neuroscience, particularly to study learned helplessness & the impact of stress controllability;

• Group 1: Escapable Stress (E)

• Group 2: Yoked-Inescapable Stress (Y)

• Group 3: Control (C)

mPFC, or more specifically, the VmPFC

What area of the brain is responsible for detecting whether stress is controllable?

DRN

What nuclei is involved in the learned helplessness response?

• Controllable stress (detected by vmPFC) inhibits the activation of the DRN

• Prevents excessive release of serotonin (5-HT) and maintains resilience/active coping mechanisms

• Prevents helplessness

How does controllable stress impact the DRN?

• Uncontrollable stress (detected by the vmPFC), excites the release of 5-HT from the DRN

• Excessive 5-HT released from overactive DRN leads to impairments in controlling motivation & escape behaviours

• Leads to passive response to stress

How does uncontrollable stress impact the DRN?

Glucocorticoids

Stress hormones released from the adrenal cortex as a part of the HPA axis stress response; most common in humans is cortisol

• Stressor occurs

• Hypothalamus activates the HPA axis

• Pituitary gland releases ACTH

• Adrenal cortex releases cortisol

Stressor → Hypothalamus → Pituitary gland (ACTH) → Adrenal cortex (cortisol)

What are the steps in Glucorticoids release?

Biphastic effect

The effect that occurs when a substance or stimulus produces two different, often opposite, effects at different concentrations or dosages.

Creates an inverted U shaped graph

E.g., Yerkes-Dodson law

• Severe or Prolonged Stress (causes large increase in Glucorticoids that stay high for long periods) is harmful to the brain, NS and body

  • Reduced neuroplasticity/neurodegeneration

  • Neuronal damage

  • Impaired PFC function

  • Memory Problems

  • Other health conditions

• Mild or Moderate Stress (small or moderate increase in Glucorticoids) is beneficial at improving attention, focus, learning, memory, and overall performance

  • Improved learning & memory

  • Increased synaptic plasticity

  • Improved attention & focus

  • Strengthen memory formation

Why are Glucorticoids biphastic?

• Large release of stress hormones (Glucorticoids)

• Over-activation of neurons

• Excess glutamate release

• Excitotoxicity (neuronal damage)

Why is excessive or prolonged stress harmful?

• Rapid (Non-genomic) Effects

  • Seconds to milliseconds

  • Glucocorticoids interact with receptors on or near the cell membrane

  • Rapid changes in NT release

  • Changes in synaptic transmission

  • Quick modulation of neural excitability

• Slow (genomic) Effects

  • Hours to days

  • Glucorticoids cross cell membrane and bind to intracellular receptors → move to cell nucleus and alter gene transcription

  • Changes in protein production

  • Altered synaptic plasticity

  • Structural changes in neurons

  • Long-term changes in learning an memory

What are the 2 main ways Glucorticoids act on the brain/body?

• Glucorticoids act through multiple mechanisms allowing stress to have short-term benefits & long-term costs (if chronic)

Why do Glucorticoids have a biphastic effect on the brain/body?

• Mobilization of energy at the cost of energy storage

• Increased cardiovascular and cardiopulmonary tone

• Suppression of digestion

• Suppression of growth

• Suppression of reproduction

• Suppression of immunity and inflammatory response

• Analgesia

• Altered cognition & sensory thresholds

What are the principal components of the stress response?

• Fatigue, muscle wasting, diabetes

• Hypertension

• Ulcers

• Psychogenic dwarfism, bone decalcification

• Suppression of ovulation & loss of libido

• Impaired disease resistance

• Apathy

• Accelerated neural degeneration during aging

What are the 8 common pathological consequences of prolonged stress?

• Excessive release of NE, E, and cortisol in circulation will reach their receptors on prefrontocortical (PFC) neurons.

• PFC neurons = overly-stimulated, releasing massive amounts of glutamate, which can cause excitotoxicity

• On pathway of excitotoxicity involves the spillover of glutamate from synaptic cleft → activate glutamate receptors outside of the synapse

• Extra-synaptic NMDA-type glutamate receptors

• These receptors have biochemical effects that damage and/or destroy neurons

Why is prolonged stress injurious to the brain?

No; not always harmful if exposures are mild and/or early in life → Can make one more capable of handling stress later in life

• Stress Immunization

Is repeated stress exposure always harmful?

• Relaxation Training

• Systematic Desensitization

• Observational learning of coping behaviours

• Cognitive rehearsal and role taking

• Play activities that familiarize children with common hospital materials, equipment and experiences

What are the five types of stress immunization training?

Relaxation Training

A type of coping strategy where people are taught techniques to reduce physiological stress responses:

• Deep Breathing

• Progressive muscle relaxation

• Mindfulness

Lower sympathetic nervous-system activation

Systematic Desensitization

A coping technique used for phobias and anxiety;

• Learn relaxation techniques

• Gradually expose person to feared situation

• Increase exposure slowly over time

Eventually the person becomes desensitized to the stressor

Observational Learning of Coping Behaviours

A coping technique where people watch others successfully cope with stress to help them learn effective coping strategies & that the situation is manageable

• Uses social learning

Cognitive rehearsal & role taking

A type of coping mechanism where people mentally practice stressful situations before they occur to reduce uncertainty and anxiety

Play Activities

A coping mechanism where children interact with hospital equipment or medical materials through play to reduce stress and the fear of the unknown

Pain

The perception/discomfort of tissue damage or threat of damage (psychogenic stress)

• Withdraw from/avoid harmful stimuli

• Protect injured tissue

• Signal danger to others

Why can pain be helpful?

Nociceptors

Peripheral receptors on free nerve endings that respond to painful stimuli

• Mechanical damage

• Extreme temperature

• Chemical irritants

What do nociceptors detect?

TRPV1

What receptor typically detects painful heat, but also reacts to capsaicin?

Spinothalamic pathway

The main pain pathway in the body

• Nerve fibres send axons into the dorsal horns of spinal cord

• Axons synapse on spinal neurons that project across the midline before ascending to thalamus

• Thalamus transmits pain input to the somatosensory cortex and the cingulate gyrus

• Glutamate and substance P are released to boost pain signals and remodel neurons

What is the path of painful sensations in the body?

Localization of pain

What is the role of the somatosensory cortex in pain?

Emotional pain

What is the role of the cingulate gyrus in pain?

• Spinothalamic:

  • Anterior: Crude touch and pressure

  • Lateral: Pain and temperature

• DCML: fine touch, vibration, and proprioception

• Spinocerebellar: Unconscious proprioception

What are the 3 ascending tracts of the anterolateral (spinothalamic) system ?

Placebo effect

Stress or pain improves after getting exposed to treatment or condition that has no theraputic benefit.

Caused by a person’s expectations or psychological states

Nocebo effect

Negative effects on pain and stress develop because of an expectation of harm

Psychogenic pain

Pain caused by emotional, cognitive or psychological processes;

E.g.,:

• Stress-induced headaches

• Pain triggered by traumatic memories

• Anxiety-related stomach pain

Also known as internally generated pain → even though the cause is psychological, pain is real and physically experienced

• Emotional component

  • Processed by emotional brain circuits

• Physical component

  • Represented in sensory brain areas (e.g., somatosensory cortex)

What are the two components of psychogenic pain?

• Hippocampus (HPC): retrieves negative memories

• Amygdala: Fear & emotional processing

• BNST: Prolonged anxiety & stress anticipation

• Prefrontal Cortex (PFC)/DRN: Cognitive interpretation of the situation (controlled vs uncontrolled stress)

• Pain typically localized in S1 (somatosensory cortex

What brain regions are involved in psychogenic pain?

• Motoric dimension

• Emotional dimension

• Cognitive dimension

• Physiological dimension

What are the 4 dimensions of pain?

Motoric dimension of pain

A dimension of pain that determines actions or behaviours triggered by pain:

• pulling hand away from something hot

• guarding an injured limb

• facial expressions of pain

• changes in posture or gait

Involves:

• PMC

• SMA

• M1

Emotion dimension of pain

A dimension of pain that determines:

• How unpleasant pain feels

Brain region:

• Cingulate cortex (Cg)

Cognitive dimension of pain

A dimension of pain that determines:

• Interpretation of pain

• Expectations of pain

Brain Region:

• Prefrontal cortex (PFC)

Physiological dimension of pain

A dimensions of pain that activates the body’s stress systems:

• Hypothalamus

• HPA axis

• SAM axis

These systems trigger physical responses such as:

• Increased heart rate

• Cortisol release

• Heightened arousal

Somatization

Manifestation of condition as real and physically experienced pain and symptoms;

associated with hyper-activation of the anterior cingulate gyrus, abnormal PFC-DRN activity, hyperactivity of the amygdala/BNST, somatosensory cortex (S1), hippocampus and insula.

Alexithymia

Reduced ability to recognize and verbalize one’s emotions, along with difficulties distinguishing bodily sensations from emotional experiences; associated with somatosensory amplification and link to activity in right cingulate, amygdala and insula

Somatoform Disorders /Somatic Symptom Disorders

Mental health conditions where individuals experience real, distressing physical symptoms (e.g., pain, fatigue, dizziness) without a fully explained medical cause

• Somatization disorder

• Conversion disorder/Functional Neurological System disorder

• Illness Anxiety Disorder (hypochondria)

• Pain Disorder

• Body dysmorphic disorder

What are the 5 main types of involuntary somatic symptom disorders?

• Factitious disorder (Munchausen Syndrome)

• Malingering (Secondary gain)

What are the 2 main types of voluntary somatic symptom disorders?

Gate Control Theory

Theory that explains how pain signals are regulated in the spinal cord before they reach the brain

• Pain signals form the body must pass through “gates” in the spinal cord

• These gates determine how much of the pain signals is allowed to reach the brain

• Pain is not a direct signal, it is modulated (adjusted) along the way

Nociceptors → afferent sensory neurons → dorsal horn of spinal cord → gating mechanisms → Thalamus → cortex

Top-down modulation of pain

The theory that suggests that pain signals can also be controlled by the brain itself, not just by the spinal cord.

• Expectations of pain drive pain experience

• Periaqueductal gray (PAG) = important structure