The Science of Stress: The Time-Dependent Multimodal Effects of Stress Hormones on Memory and Learning

Dr. Beth Baldwin Monday, June 24, 2024

According to the American Institute of Stress, 55% of people in the United States experience daily stress. Stress is, technically defined as the body's nonspecific response to any demand – pleasant or unpleasant – but more commonly perceived as a state of physical, mental, or emotional strain or tension. Chronic stress is especially prevalent in the workplace, with 83% of employees reporting daily work-related stress (1). However, statistics show that stress among students is also significant, common, and increases proportionally to a student’s progress through the educational system.

Recent studies on academic pressure found that three-quarters of American high schoolers and half of middle schoolers described themselves as “often or always feeling stressed" by schoolwork (2). Meanwhile, at American colleges, over a third of students say they’ve considered withdrawing from their program for at least one term, and over half of those cite emotional stress as the primary reason (3).

And yet – not all stress is negative. Some stress is not only unavoidable but may actually be necessary to motivate and enable learning, retention and updating of information. Research has found that stress affects our memory through numerous mechanisms, each with different impacts. While the link between chronic excessive stress and cognitive decline in aging brains has been well established, the variable effects of different stress hormones on memory and learning in younger people have received far less attention to date.

This information may be key to helping learners of all ages understand and manage the impact of the type and timing of stress on their ability to be successful in meeting their educational and career goals. Within the medical community, understanding the hormone connections to learning and memory may help providers to better support patients experiencing elevated stress levels.

The Science of Stress

The two major stress systems have both been shown to be critical for the modulation of learning and memory processes. The autonomic nervous system (ANS) response is rapid and involves the release of catecholamines norepinephrine and epinephrine from the adrenal glands and the brainstem in a matter of seconds. This is how the sympathetic nervous system prepares the body and brain for a ‘fight or flight response,’ dilating the pupils and bronchi while constricting blood vessels and accelerating heart rate. The ANS also rapidly affects neural functioning in multiple brain regions including the amygdala, hippocampus, and pre-frontal cortex, with profound effects on attention, working memory and long-term memory.

The second stress response by the hypothalamic-pituitary-adrenal (HPA) axis is slower, effectively operating on a delay. In response to ANS signaling, the hypothalamus releases corticotropin-releasing hormone (CRH) which stimulates the anterior pituitary to secrete adrenocorticotropic hormone (ACTH), triggering the release of glucocorticoids from the cortex of the adrenal gland – primarily cortisol, a steroid hormone. Levels of cortisol peak about 20 to 30 minutes after the onset of the stressor and bind both glucocorticoid and mineralocorticoid receptors (MR) in the body and brain (4).

Glucocorticoid receptors (GR) are widespread throughout the brain, while MR is primarily expressed in regions associated with memory and emotion - specifically the amygdala, hippocampus and pre-frontal cortex. This allows cortisol to have two separate and opposite modes of action within the brain. Cortisol binding to the MR quickly increases neural excitability in the amygdala and hippocampus, while GR binding has a slower effect, developing over 60-90 minutes after the onset of the stressor, and causes changes to DNA translation and transcription to re-establish homeostasis and calm the neural excitability caused by the acute effects of stress.

This complex symphony of hormones explains why stress can have significant effects on memory that vary by timing of stressor, memory and the type of information being learned.

Fig. 1 The Stress Response System

Stress During and Around the Time of Learning Actually Enhances Memory

Moderate stress just before, during or just after encoding and consolidating new information may strengthen human memory formation.
The release of norepinephrine and cortisol activate the amygdala and hippocampus to enhance emotional processing, memory, and learning.
In particular, stress can lead to better memory for emotionally charged events or for information directly related to the stressor, through norepinephrine's activation of a brain network known as the salience network, which includes the amygdala.
This type of memory enhancement is norepinephrine-dependent and can be disrupted by the beta blocker propranolol, which is currently under study for prevention and treatment of Post-Traumatic Stress Disorder (5).
For example, showing an emotionally arousing, contextually related film before a lesson may enhance encoding and consolidation of pertinent information as a memory.

Stress Long Before Learning or in a Different Context Impairs Memory

In studies, encoding of new information was impaired when a stressor occurred more than 30 minutes before learning, or in a distinctly different context (for example, stress occurring at home versus in the classroom).
This may be attributable to the decrease in hippocampal neural excitability as a late effect (>1 hour) of cortisol exposure, which is theorized to protect the consolidation of the information learned during the stressful encounter, versus allowing new memories to form.
Chronic or excessive secretion of stress hormones can negatively impact long-term memory via structural and functional changes to the hippocampus, a brain region crucial for memory consolidation.

Cortisol Impairs Memory Retrieval

During memory retrieval, such as recall of information during an exam, high cortisol levels can hinder performance.
This effect was observed beginning 20 minutes after a stressor, when cortisol is at peak levels, and was even more prominent during the time when cortisol exerted its longer-acting genomic mode of action.
Cortisol-induced retrieval deficits were found to impact both adults and children aged 8-10, with broad significance for educational assessment of information learned.
Interestingly, context modulated this effect, so that recall was not impaired significantly by stress if the test information was relevant to the stressful situation, or if the learning and the test occurred in the same context.

Stress Hormones Impact Knowledge Updating, Cognitive Flexibility, and Goal-Directed Behavior

Reconsolidation theory suggests that consolidated memories return to a malleable state when they are reactivated. During reconsolidation, which takes place in the hippocampus and prefrontal cortex – key targets of stress hormones - memories may be weakened, strengthened, or altered.
While investigations are still underway, animal studies suggest that stress or cortisol exposure after memory reactivation impairs reconsolidation.
Misinformation studies in humans have also found that highly arousing information learned under stress results in more robust memories that are less susceptible to being updated. This may have negative implications for education, professional learning, and life experiences that require frequent updating of knowledge based on new information.
Under stress, cortisol’s action at the MR appears to shift human behavior toward habit, relying on more rigid striatal stimulus-response learning strategies rather than the cognitive hippocampal memory system. This system allows for the formation and recall of flexible memories and underpins goal-directed (action-outcome) behavior.

Balancing Stress Hormones is Essential for Cognitive Health

Optimal memory function requires a balance in stress hormone levels. Normal physiological responses to moderate acute stress can be beneficial for memory, but chronic stress and elevated cortisol levels are harmful.
Strategies like exercise, mindfulness, strong routines, emotional regulation, and adequate sleep can help regulate stress hormones and support memory and learning (4).

In summary, stress hormones can be a double-edged sword when it comes to memory and learning. In addition to the timing of stressors, individual perceptions of and responses to stress vary, and some people may be more resilient than others.

Fortunately, for anyone concerned about how stress may be impacting memory, attention or learning, saliva cortisol testing - considered the gold standard in cortisol assessment - is readily available from ZRT Laboratory. Alternatively, dried urine diurnal hormone testing may be used to assess cortisol and cortisone, as well as the catecholamines norepinephrine and epinephrine, which are needed in the right amounts at the right time of day to facilitate learning and memory formation. Either test involves collecting four non-invasive samples over the course of a single day to generate a four-point diurnal curve. This information allows health care providers to pinpoint any issues within the sympathetic nervous system and HPA axis that may be contributing to difficulties with attention, focus, memory, learning, and more. Utilizing convenient at-home stress hormone testing can help provide meaningful insights into a patient's health to support a path towards optimal memory, learning, and achievement of goals.

Fig. 1: Learning and Memory Under Stress

Figure 2. The effects of stress on memory depend on the specific memory process investigated and the temporal proximity between the stressful event and this memory process. While stress (indicated as red flash) long before encoding impairs memory formation, stress shortly before or after the presentation of new information generally enhances subsequent memory performance. In sharp contrast, stress before memory retrieval impairs the recall of information learned previously which may directly affect performance at exams. In education, knowledge needs to be frequently updated by new facts or concepts relating to prior knowledge. In addition to its effects on memory encoding and retrieval, stress appears to impair this integration of new information into existing knowledge structures (6).

Image credit: Vogel, Susan & Schwabe, Lars. "Learning and memory under stress: implications for the classroom." npj Science of Learning, Jun 29, 2016. npj Science of Learning.

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