JD

Emotion and Stress

Emotion (Mostly Fear)

  • Aversive Stimulus (US): Leads to conditioned emotional responses.
  • Tone (CS): Paired with the US to strengthen synapses.
  • Lateral Nucleus: Receives sensory information.
  • Central Nucleus: Becomes active in response to threatening stimuli, triggering conditioned emotional responses via the hypothalamus, midbrain, pons, and medulla.
  • Basal Nucleus: Involved in learning fear associations.
  • Synapse Strengthening: Occurs due to the pairing of the CS and US.

Review: Arcuate Nucleus Anatomy

  • Bidirectional Regulation: Two cell types work together to regulate intake.
  • Cell Types: Named according to the neuropeptides they release.
    • NPY/AgRP: Promote intake/hunger by releasing NPY and AgRP.
    • POMC/CART: Inhibit intake/promote satiety by releasing α-MSH, CART, and β-endorphin (an opioid).
  • Projections: Both NPY/AgRP and POMC/CART project to the lateral hypothalamus (LH) and release neuropeptides onto neurons that release orexin or MCH. Neurons in this region (and the PVN) also have MC4 receptors.

Non-Homeostatic Factors: Cognitive & Emotional

  • Homeostatic vs. Hedonic: Distinction between homeostatic hunger/satiety and hedonic signals influencing food intake.
  • Affective Signals: Cues signal food.
  • Positive Reinforcement: Eating as a reward.
  • Negative Reinforcement: Eating as relief of a negative emotional state.

Non-Homeostatic Factors: Reward

  • Dopamine (DA) Pathways:
    • Nigrostriatal: SNC → Dorsal Striatum
    • Mesolimbic: VTA → limbic areas
    • Mesocortical: VTA → cortex
  • Neurotransmitters: Many are important for reward-related signaling, including opioids, orexin, serotonin, endocannabinoids, and cues.

Dopamine and Conditioning

  • Pavlovian & Operant Conditioning: DA neurons signal reward information.
  • Timing of Reward: Sensitive to the timing of reward delivery.
  • Behavioral Responses: Follows the shift in behavioral responses.
  • Phasic Responses: Occur to unexpected rewards.

Dopamine and Reward Magnitude

  • Reward Magnitude Coding: DA neurons code reward magnitudes at reward receipt and at cues.

Orexin and Reward System

  • Homeostatic/Hedonic System Overlap: Rewards and cues can activate orexin.
  • Engagement: Orexin engages the reward system and areas activated by rewards, also innervated by DA.

Review of Eating Regulation

  • Homeostatic Control: Peripheral signals (ghrelin, leptin, insulin, GLP-1, CCK), hypothalamus (ARC: POMC, CART, AgRP, NPY), LHA (Orexine, MCH), PVN (CRH, OT).
  • Hedonic Control: VTA, N. accumbens (mesolimbic dopaminergic system), Dorsal striatum.
  • Eating Behavior: Dependent on both homeostatic and hedonic regulation.

Brain Areas and Feeding

  • Multiple Areas Involved: Feeding is also controlled by areas important for reward, taste, cognition, and memory.

Obesity Epidemic in the United States

  • Health Risks: Confers increased risk of Type 2 Diabetes & Heart Disease.
  • Comorbidity: Often comorbid with depression, anxiety, compulsivity, and binge eating disorder.
  • Important Considerations:
    1. BMI Imprecision: BMI is imprecise.
    2. Wholistic Well-being: Psychological body shaming can be devastating to health.

Outline of Topics

  • Defining emotion
  • Amygdala involvement in expression and recognition of fear
  • Prefrontal regulation of fear expression
  • Insula & disgust
  • Competing theories of feeling emotion

Emotion

  • Definition: Positive or negative reactions to a situation with patterns of physiological changes, behaviors, and feelings.
  • Basic Emotions: Anger, fear, surprise, disgust, joy, and sadness (according to Ekman).
  • Universality: Are all emotions universal?
  • Communication: How/why do we communicate our emotions?

Components of an Emotional Response

  • Behavioral: Muscle movements appropriate to the situation.
  • Autonomic: ANS actions facilitate behavior and quick mobilization of energy; engagement of sympathetic and quieting of parasympathetic.
  • Hormonal: Actions of hormones that reinforce autonomic responses.

Efferent Nerves of the Autonomic Nervous System

  • Sympathetic Nervous System: Prepares the system for intense physical activity; "fight or flight."
  • Parasympathetic Nervous System: Opposing effects; slows energy functions; "rest-digest."

Studying Emotions in Animals

  • Operationalization: Make the unmeasurable measurable by identifying a behavioral output that accompanies the emotion.
  • Focus Emotions: Fear (Amygdala), Disgust (Insula).

Brain Areas Involved in Emotion and Fear

  • Emotional Experience: Limbic system (amygdala, cingulate cortex, hippocampus) & insula.
  • Executive Control/Regulation: Prefrontal cortex.

Fear & Amygdala

  • Adaptive Emotional Response: Coordinated by the nuclei of the amygdala.
  • Amygdala Regions:
    • Basal and Lateral Nuclei: Important for learning fear associations.
    • Central Nucleus: Becomes active in response to threatening stimuli.

Fear Conditioning

  • Definition: The most basic form of emotional learning is a conditioned emotional response.
  • Signaled US: Shock → UR (freeze); CS (context & tone) → CR (freeze).
  • Unsignaled US: Shock → UR (freeze); CS (context) → CR (freeze).
  • Species-Typical Fear Responses:
    • Rodents: Freezing, darting, startle.
    • Humans: Startle, fleeing, fighting, fearful facial expressions, crying, and elevated heart rate.

Amygdala and Fear Conditioning

  • Synaptic Changes: Pairing a tone (CS) with a foot shock (US) strengthens synapses in the lateral amygdala, leading to conditioned emotional responses controlled by the hypothalamus, midbrain, pons, and medulla.

Fear Conditioning and LTP in Lateral Amygdala

  • LTP: Fear conditioning drives LTP in the lateral amygdala.
  • Increases: EPSPs & number of AMPAR.
  • Blocking: Blocking steps of LTP in the lateral amygdala (blocking AMPAR insertion or NMDAR function) prevented the establishment of fear conditioning.

Lesioning the Amygdala

  • Prevents Fear-Related Behavior: Patients with Urbach-Wiethe disease, which causes bilateral amygdala destruction, show a reduced sense of danger, distrust, and lack of fear and anger.

Amygdala and Recognition of Fear Expressions

  • Eye Fixations: Patients with amygdala damage do not look at the other person’s eyes and have altered eye fixations.

Amygdala and Visual Information

  • Emotional Blindsight: Amygdala receives visual information from subcortical pathways.
  • Blindsight: People are still able to process visual stimuli despite being cortically blind.
  • Affective-Blindsight: Ability to process bodily and facial expressions.

Inhibition of Fear Responses

*How are innate or conditioned fear responses inhibited?

vmPFC and Extinction

  • Extinction: Loss of association between the CS and the US; a new form of learning where the expression of the CR is inhibited.
  • vmPFC: The ventromedial prefrontal cortex supplies that inhibition.
  • Lesions: Lesions of the vmPFC impair extinction.
  • Stimulation: Stimulation inhibits the conditioned emotional response.

Changes in Emotion Circuitry During Fear Learning and Extinction

  • Fear Acquisition: Strengthening of CS synapse in LA.
  • Fear Extinction: Pathways from vmPFC to the central amygdala are strengthened, allowing for inhibition of motor output.

Changes in Emotion Circuitry During Fear Extinction vs. "Forgetting" (Reconsolidation)

  • Extinction: New learning creates a second memory trace.
  • Forgetting: When a memory is reactivated, it is in a fragile state that allows it to be disrupted, altered, or erased before it is reconsolidated.

Disgust & Insula

  • fMRI Study: Both smelling a disgusting odor and seeing a face of a person showing an expression of disgust activate the insular cortex.
  • Damage: Damage to the insular cortex and basal ganglia impair people’s ability to recognize facial expressions of disgust.

Components of Emotional Response

  • Behavioral: Muscle movements that are appropriate to the situation that elicits them.
  • Autonomic: ANS actions facilitate behavior and quick mobilization of energy; engagement of sympathetic and quieting of parasympathetic.
  • Hormonal: Actions of hormones that reinforce autonomic response.

Theories of Feeling Emotion

  • Feedback: Emotion-producing situations elicit physiological responses and behaviors & the brain receives sensory feedback from the muscles and organs, which produces the emotional responses. The feedback IS the feeling.

Stress and Anxiety Disorders

  • Hypothalamus: Releases corticotropin-releasing hormone (CRH).
  • Anterior Pituitary Gland: Releases ACTH (adrenocorticotropic hormone).
  • Adrenal Cortex: Releases glucocorticoids.
  • Adrenal Medulla: Releases epinephrine and norepinephrine.
  • Neuron of Sympathetic Nervous System.

Human Equivalents – Exploring a Soccer Field for 15 min

  • Walz et al. (2016) - 4 groups:
    • 16 patients with agoraphobia vs 16 healthy controls
    • 18 healthy individuals with a risk for agoraphobia (i.e., high anxiety sensitivity) vs 19 individuals with low anxiety sensitivity

Theories of Feeling Emotion

  • Feedback: Emotion-producing situations elicit physiological responses and behaviors & the brain receives sensory feedback from the muscles and organs, which produces the emotional responses. The feedback IS the feeling.

vmPFC Role in Extinction

  • Inhibition: vmPFC supplies inhibitory input to the amygdala.
  • Extinction: Loss of association between the CS and the US.
  • Lesions: Lesions of the vmPFC impair extinction.
  • Stimulation: Stimulation of vmPFC inhibits the conditioned emotional response.

Stress

  • Definition: The word can be a noun or a verb, and the noun can refer to situations or the individual’s response to them.
  • Exposure: When someone was subjected to stress, they were exposed to a situation that elicited a particular reaction: a stress response.
  • Types of Stressors: Physical, psychological, and environmental; acute or chronic; prenatal, early life, vs. adulthood.
  • Stress Responses:
    • Sympathetic adrenal-medullary (SAM) system.
    • Hypothalamic Pituitary Adrenal (HPA) axis.

Anatomy of the Adrenal Gland

  • Adrenal Gland: A small organ located on top of each kidney
  • Components:
    • Adrenal Cortex: Zona glomerulosa (Aldosterone), Zona fasciculata (Cortisol), Zona reticularis (Androgens)
    • Adrenal Medulla: Epinephrine

Sympathetic Adrenal-Medullary (SAM) System

  • Pathway: Forebrain and hindbrain neurons activate the sympathetic nervous system efferent nerves, which stimulate the adrenal medulla to release epinephrine & norepinephrine into the body & brain.
  • Mechanism: Rapid activation of the sympathetic nervous system.

Hypothalamic Pituitary Adrenal Axis (HPA)

  • Pathway: Paraventricular nucleus of hypothalamus (PVN) releases CRH onto the anterior pituitary gland, which releases ACTH onto the adrenal cortex, which releases glucocorticoids to act on body & brain.

Pituitary Gland

  • Process: PVN hypothalamic cells release hormones (CRH) that enter the capillaries. The capillaries convey the hormones to the anterior pituitary, where they stimulate the secretion of additional hormones (ACTH) to act on the adrenal cortex.

Outputs of the Central Nucleus of the Amygdala

  • The amygdala & hypothalamus engages the stress response. Many brain regions receive input from the central nucleus of the amygdala and the emotional responses controlled by these regions.

Mobilizing Body and Brain

  • SAM System: rapid activation of the sympathetic nervous system.
  • HPA Axis: Release of glucocorticoids,Adrenaline/noradrenaline.
  • Glucocorticoids: Glucocorticoids help regulate glucose metabolism & immune function.

Acute vs. Chronic Stress

  • Acute Stress: Adaptive to a point.
  • Chronic Stress: Often leads to poor health.
    • Harmful effects of stress are produced by prolonged secretion of glucocorticoids and suppression of the immune system.
    • High blood pressure caused by epinephrine and norepinephrine.
    • Impaired regulation of the HPA axis.

Bereavement and Immune System

  • Bereavement can suppress the immune system. Husbands of women who died of breast cancer had lowered immune responses after their wive’s death.

Chronic Stress and Brain Damage

  • Glucocorticoids: Long-term exposure destroys neurons located in the hippocampus.
  • Stressors throughout our lives increase the likelihood of memory problems as we grow older

Early Life Stress and Prefrontal Cortex

  • Dorsomedial Prefrontal Cortex: The volume of the dorsomedial prefrontal cortex was reduced 7.2 percent in people who experienced emotional maltreatment during childhood.
  • Rodent studies have also found prenatal and early life stress to alter volume and functioning of the hippocampus and lateral amygdala

Stress Resilience

  • Individuals are resistant or resilient to stress effects, despite evidence that stress can damage the brain.

Psychiatric Disorders

  • Definition: Characterized by psychological and behavioral symptoms that impact many areas of life. Share underlying genetic risk factors and neural mechanisms.

Posttraumatic Stress Disorder (PTSD)

  • Characteristics: Recurrent dreams or recollections of the traumatic event, feelings that the traumatic event is recurring, intense psychological distress.
  • Genetic & Environmental Factors: development is increased if traumatic event involved danger or violence from other people, Increased with the number of traumatic events, COMT (Val 158Met, enzyme that metabolizes catecholamines, Shared genetic factors between PTSD and other mental health disorders and behavioral tendencies.

Hippocampus and PTSD

  • HPC is thought to be important for regulating fear responses by helping distinguishing safe from dangerous contexts. PTSD associated with a smaller hippocampus. Twin studies suggest that the size of the HPC may predate the exposure to stress and confer susceptibility to PTSD.

Brain Areas Involved in Fear, Stress, & Anxiety

  • Emotional experience & behavior production: Limbic system (amygdala, cingulate cortex, hippocampus) & insula.
  • Executive control/ regulation of the emotion: prefrontal cortex (vmpfc)

PTSD: Amygdala and Medial Prefrontal Cortex

  • Increased amygdala response to fearful faces and decreased prefrontal cortex activity in response to fearful faces.

PTSD Treatments

  • Therapies: Cognitive behavioral therapy, group therapy, antidepressants.
  • Neurobiological Treatments: TMS of the dlPFC, cortisol administration immediately following trauma, drugs to alter memory consolidation, propranolol (beta adrenergic receptor antagonist).
  • Low-dose Cortisol: thought to help enhance consolidation of new, positive association and reduce emotional significance of trauma

Anxiety Disorders

  • Definition: Characterized by unrealistic, unfounded fear and anxiety.
  • Fear vs. Anxiety: Immediate danger vs. not immediate (preparatory).
  • Common Psychiatric Disorders: Contribute to the occurrence of depression and substance abuse disorders.
  • Include: Generalized anxiety disorder, panic disorder, phobia-related disorders, agoraphobia, social anxiety disorder.

Brain Areas Involved in Anxiety Disorders

  • fMRI studies suggest that the emotion areas (amygdala & cingulate, prefrontal, and insular cortexes) are involved in anxiety disorders. Hyperactivation of the “fear network” and hypoactivation of the executive control/ regulation of the frontal cortices.
  • amygdala and insular cortex activity and decreased prefrontal cortex

Treatments for Anxiety Disorders

  • Benzodiazepines: GABAA receptor agonists; for emergency medical treatment; rapid onset, but potential for abuse.
  • Amygdala: Amygdala contains high levels of GABAA receptors.
  • SSRIs: selective Serotonin reuptake inhibitors; slower acting; used to treat anxiety and depression.

Testing Anxiety in Rodents

  • Approach-Avoidance Tasks: Exploratory paradigms.
  • Anxiety-Like Behavior: Spending less time in the open spaces or Open Field Test elevated Zero Maze.
  • Predictive validity: Animals given benzodiazepines spend more time in open space.