12 01neurLecture 4 ; Sept 19, 2013Stress

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Book recommendation

Why Zebras Dont Get Ulcers Robert M. Sapolsky

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What is stress? Stressors are a stimulus that challenges

the bodys homeostasis and triggers a response. Stressors may be psychological or

physical. They may represent real, perceived, or imagined threats. If a stimulus causes a stress response, it can be considered a stressor.

The stress response is the bodys response to the challenge of a stressor. The stress response involves physiological

and behavioral changes that attempt to cope with or escape the stressor.

All stressors (psychological or physiological) produce a similar pattern of physiological changes.

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Stress is an everyday event While major stressors (war, disaster,

death, divorce, etc.,) are clearly problematic, researchers are finding that minor stressors (waiting in line, paying bills, other daily hassles,) add up as well.

Additionally, major stresses can produce minor stresses The major life event divorce can lead to a

lot of smaller hassles: finding a lawyer, separating belongings, moving, arguing, etc.,

Routine, daily stresses may have a significant impact on health. This may be an especially big problem in modern times, when daily hassles are inescapable.

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Behavioral and psychological eects Impaired task performance.

choking under pressure. Burnout.

Physical, mental and emotional exhaustion due to long-term involvement in stressful situations.

Post-Traumatic Stress Disorder (PTSD). Can be caused by war, rape, natural disasters, etc., Involves invasive memories of the trauma, nightmares, flashbacks,

anxiety, etc., Other psychological disorders.

Depression, anxiety, problems with sleep, exacerbation of other mental illnesses.

Positive eects. Stress does help us confront our troubles. Overcoming stressful

situations may also yield a new lease on life.

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The physiological response to stress Hans Selye (1907-1982) is often credited with

being the first scientist to characterize the concept of stress.

He proposed a three stage model called general adaptation syndrome. Alarm: Initial reaction to stressor. Fight or flight

(SNS) activated. Resistance: Physiological adaptations take place

to help cope with prolonged stressors. Involves cortisol and the HPA axis.

Exhaustion: Physiological resources are depleted as the body becomes unable to cope with the prolonged stressor. This is where diseases can begin to appear.

This basic progression is the same regardless of the type of stressor. Physical and psychological stressors of all types produce these eects.

Hans Selye

Stress was originally a term borrowed from engineering.

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The physiological response to stress The stress response involves two

separate pathways:

The sympatho-adrenomedullary axis (SAM axis) The fast pathway Mediates the initial alarm phase of the

stress response.

The hypothalamic-pituitary-adrenal axis (HPA axis) The slow pathway Mediates the physiological adaptations

involved in dealing with prolonged stress.

The SAM axis is important in dealing with short-term surprises.

The HPA axis is involved in long-term stressors, for example schoolwork.

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The adrenal gland

The adrenal glands - of or near kidney (L.) sit atop the kidneys. The adrenal glands are critical for the stress response.

The adrenal glands are actually two glands in one. The adrenal medulla secretes epinephrine (aka adrenalin) and norepinephrine (aka noradrenalin). The adrenal cortex secretes cortisol.

Adrenal medulla!

Adrenal cortex!

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The SAM axis the fast pathway There are two steps in SAM activation:

1. Neural circuits in the hypothalamus project to the spinal cord, where they synapse with neurons of the sympathetic nervous system (SNS).

2. SNS neurons project to the adrenal medulla. The adrenal medulla releases the catecholamines epinephrine and norepinephrine into circulation.

Eects of epinephrine and norepinephrine: Increases heart rate, blood pressure,

glycogenolysis, and lipolysis (releases sugar and fat into blood stream).

Hypothalamus!

Spinal cord!

Adrenal medulla!

Adrenaline & noradrenaline!

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The HPA axis the slow pathway There are three steps in HPA axis

activation:

1. The hypothalamus releases corticotropin-releasing hormone (CRH) into the anterior pituitary (AP).

2. CRH stimulates the AP to release adrenocorticotropic hormone (ACTH) into general circulation.

3. ACTH stimulates the release of cortisol from the adrenal cortex.

Eects of cortisol: Increases fat and protein catabolism,

raises blood sugar, suppresses immune system and inflammation.

Hypothalamus!

CRH !

ACTH! Cortisol!

Ant. pituitary!

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How does stress impair cognition? If the stress response is designed to help us

in times of crisis, why does it seem like our brain always fails us when we need it?

Researchers began studying this eect after they noticed that extremely skilled WWII pilots often crashed their planes during the stress of battle.

It seems that the stress response tends to

suppress higher level reasoning, flexible thinking, and memory. Stress also increases anxious, fearful thinking.

On the other hand, stress can improve

performance in simpler, well-rehearsed tasks.

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How does stress impair cognition? The prefrontal cortex (PFC) is

the most recently evolved brain structure in humans. It matures in early adulthood.

The PFC is involved in concentration, planning, decision making, insight, judgment, error detection, and memory retrieval.

PFC function is negatively aected by stress.

Frontal lobe!

Prefrontal cortex!

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Stress and the prefrontal cortex Under baseline conditions, the PFC

helps us think our way out of problems. It acts as a control center, keeping our impulses in check.

Stress weakens this influence, allowing older and more primitive parts of the brain to become dominant. These regions are not specialized for

complex thinking. Instead, they favor inflexible, impulsive behaviors and thoughts.

Under the influence of these regions, we may become consumed by anxiety, or give in to impulsive behaviors (drugs, food, drink, etc.)

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How does stress impair cognition? Studies that experimentally

manipulated stress levels showed that:

Stress impairs performance of tasks that require complex, flexible thinking. These involve the PFC.

Stress seems to improve performance of simpler/well rehearsed tasks. These involve the basal ganglia and parts of the limbic system (the amygdala in particular). The basal ganglia are a ground of subcortical nuclei involve

in motor control, learned behaviors, and motivation.

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Subcortical areas involved in stress

Amygdala: Emotions/fear

Hypothalamus: Autonomic response

Basal ganglia: Habits, impulses/

cravings

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How does stress impair cognition?

At baseline, inhibitory projections from the PFC exert top-down control over lower brain areas. This allows higher level cognitive function to suppress impulsive behaviors and emotions.

Under stress, dopamine and norepinephrine from brainstem nuclei shut down these inhibitory projections. This suppresses the PFC, and allows lower brain areas such as the amygdala and basal ganglia to exert bottom-up control.

PFC!

Dopamine!

Norepinephrine!

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How does stress impair cognition? Under stress, pre-synaptic dopamine

and norepinephrine receptors on PFC neurons are stimulated by their respective neurotransmitters.

This causes a pre-synaptic ion channel to open, suppressing the ionic changes associated with post-synaptic potentials.

Because of this, synapses in the PFC are inhibited. PFC function is thereby reduced, as messages can no longer be processed.

Baseline PFC synapse

Stressed PFC synapse

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Why does stress impair cognition? What possible benefit could there be to

shutting down cognition in times of stress? Why would such a trait evolve?

It seems that by activating the basal ganglia and its simpler, more impulsive behaviors, the stress response allows animals to fall back on tried and true behaviors to escape trouble.

Similarly, by activating the amygdala and other limbic regions, the stress response causes animals to see everything as a threat of some kind. This is probably useful in environments where everything is a threat.

For creatures with simple brains living in

simple environments, this may be a useful tradeo.

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Chronic stress is unhealthy The stress response evolved to deal

with short-term emergencies. In the wild, stressed animals either succeed in escaping their stressor or they are eaten.

In the short term, the stress response leads to adaptive changes that help the animal respond to the stressor. To escape a predator, the animal can

afford to temporarily suspend growth, tissue repair, and immunity in order to provide energy for escape.

In the long term, these changes can be maladaptive. Chronic stress can lead to over-secretion

of cortisol. This can be associated with depression, as well a variety of other stress-related pathologies.

The stress response helps with lifes problems. Ideally once the animal escapes, the stress response can end.

The stressors faced by modern humans are not easily escaped. They come in rapid succession and relaxation is difficult to find.

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Stress and disease Prior to the 20th century, contagious

diseases were the greatest threats to health. Smallpox, diphtheria, tuberculosis,

bubonic plague, etc.,

Antibiotic medications, vaccines, as well as improvements in nutrition and hygiene have obliterated many of these diseases.

While lifespans have improved dramatically since the eradication of these diseases, chronic disease has emerged as a new threat.

A man suffering from smallpox.

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Stress and disease

While infectious diseases are on the decline, chronic diseases such as heart disease and cancer are on the rise. These diseases are dicult to cure, but they are heavily influenced by stress, so they may be somewhat preventable.

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Shutting down the stress response Cortisol secretion is regulated by a

negative feedback loop. When this system is healthy, cortisol levels never stay too high for too long.

1. The hippocampus, hypothalamus, and anterior pituitary are all sensitive to circulating cortisol.

2. When cortisol levels start to get too high, these regions work to shut down cortisol secretion.

a. The hippocampus and hypothalamus work to reduce CRH secretion.

b. The anterior pituitary secretes less ACTH.3. When CRH and ACTH secretion is

reduced, the adrenal glands produce less cortisol, thus ending the stress response.

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Hippocampus!

Hypothalamus!

Ant. Pituitary!Cortisol!

CRH (reduced)!

ACTH (reduced)!

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Neural eects of chronic stress

The hippocampus can be damaged by excessive or prolonged exposure to cortisol.

This contributes to a breakdown in the negative feedback loop that controls cortisol secretion.

Control! Daily CORT !

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Breakdown of negative feedback

CRH!

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Stress is not all bad Eustress good stress (G.) describes experiences

perceived as positive challenges rather than a threat per se. Contrast with distress.

Stress can promote personal growth or self-improvement.

Performance on tasks is best with a moderate, optimum level of arousal and stress. Too much or too little stress seems to impair performance. This relationship is called the Yerkes-Dodson law.

Psychological resilience the ability to cope with

stressful events is improved by routinely conquering stressors. This is especially true in young children. Their success in

life depends a great deal on their resilience, and resilience is shaped by successfully overcoming challenges.

The Yerkes-Dodson law