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Mechanism Involved in Contribution of Cortisol Elevation to Memory Facilitation


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Mechanism Involved in Contribution of Cortisol Elevation to Memory Facilitation

Mary Ellen Langston
2006

         The study by Abercrombie, Speck, and Monticelli (2006) elicited the effects of stress and emotion on the body to determine their roles in memory formation. Thirty-one men were subjected to a stressful event, and cortisol levels and memory retention were measured. Researchers hypothesized that stress accompanied with heightened emotion would result in elevated endogenous cortisol. They also hypothesized enhanced memory in participants who experienced higher levels of stress. Results demonstrate a positive relationship between cortisol levels and memory performance in participants with increased negative emotion.

            When subjects were shown pictures that elicited negative emotion, they remembered the event better than neutral information. Subjects carried this negative affect into the stressful event, and the negative emotion impacted their ability to recall encoded information. Studies have shown that a complex relationship exists among emotions, specific brain regions, and memory. Emotions impact memory encoding, memory consolidation and memory retrieval and are involved in producing stress hormones such as cortisol (McPherson, 2006). It appears that the amygdala is alert to negatively-charged experience. LeDoux (1996) theorizes that systems of brain structures (i.e., hippocampus, hypothalamus, amygdala, cortex, and sympathetic and parasympathetic nervous systems) interact in the relationship between emotion and memory.

Interaction Between Cortisol and Hippocampal Modulation of Emotional Arousal     

             In the study by Abercrombie et al. (2006), elevations in cortisol affect storage of emotional information rather than neutral information, and cortisol’s effects on memory are most likely to occur in states of high negative emotion (i.e., high arousal). Abercrombie (2001) also studied the effects of cortisol on explicit memory by dosing 90 subjects with either hydrocortisone (identical to cortisol) or placebo. Hypotheses included (a) low doses of hydrocortisone would enhance memory formation, (b) high doses would impair memory, and (c) hydrocortisone would have no impact on implicit memory or vigilance. In another article regarding this investigation, Abercrombie, Kalin, Thurow, Rosenkranz, and et al. (2003) summarize the study’s findings and discuss the inverted-U quadratic trends in memory recognition of negative and neutral presentations. This inverted U-shaped function describes the relationships among (a) glucocorticoids (i.e., cortisol), (b) long-term potentiation, (c) prime burst potentiation, and (d) hippocampal excitability. The study’s dose-response curve reflects lower levels of cortisol elevation enhancing memory, and higher doses reducing recall, and this correlates with negative stimuli. 

Role of the Amygdala in Memory Formation

            The amygdala is essential to emotional memory as it determines the emotional significance of events and communicates this information to other brain regions. Cortisol is the modulating factor in predicting recall of emotional memories. A strong, positive relationship exists between the amygdala’s mediation of memory retention and the effect of cortisol on the emotional memory. Cortisol affects noradrenergic processes, and amygdala activation influences cortisol’s effects on memory.

            Β-adrenergic activation is necessary for release of cortisol; therefore, testing of amygdalar activation is important in the study of mechanisms of the stress response. Cahill, Babinsky, Markowitsch, and McGaugh (1995) report that subjects’ ability to consistently remember emotional information better than neutral information is dependent on activation of β-adrenergic receptors.  Memory encoding involves the amygdala when emotion-laden memories are present, and the hippocampus, through cortisol’s effects, facilitate memory storage. In the study by Abercrombie et al. (2006) the relationship between cortisol and memory existed only in the presence of negative emotion. As amygdalar activity is increased, the impact of cortisol on memory formation increases. In a study involving 30 subjects, Southwick et al. (2002) show that adrenergic modulation is necessary for the formation of emotional memories. This study also demonstrates that increased norepinephrine involvement facilitates enhanced long-term recall.   

            Studies show that stressful conditions and high levels of emotion affect memory formation. Biochemical mechanisms involved in the stress response facilitate the release of cortisol; however, its effects are dependent on dose, chronicity, and other factors. Research findings demonstrate that emotional information is better remembered than neutral information. PET scans indicate that metabolic rates in the right amygdala during emotional events predict long-term recall (Abercrombie, 2001, p. 10).

Stress Response and Physiological Mechanisms 

            The physiological mechanisms involved in the stress response and in emotion modulation include the limbic system and hormonal secretion of epinephrine and cortisol. Networks of associations exist in neuronal connections, and memory formation occurs as synaptic connections are strengthened. Memories are permanently stored when neurons repeatedly relay information and overlapping firing occurs. Long-term potentiation is mediated by neurotransmitters, and glutamate, GABA, acetylcholine, epinephrine, norepinephrine, dopamine, and serotonin are all involved in the mediation between emotion and memory (Abercrombie et al., 2006).

             Zautra (2003) discusses the physiological changes that occur before, during, and after an individual experiences stress. Areas of the brain involved in the stress response include the hypothalamus, locus coeruleus, and the amygdala. Two systems are involved in a bi-directional feedback loop: the sympathetic-adrenal-medulla axis (SAM), which is activated at the immediate point of stress (i.e., 10 seconds) and the hypothalamic-pituitary-adrenal cortex (HPA axis), which responds later (i.e., 10 minutes). These two systems communicate with and influence the rest of the body, either stimulating or inhibiting function. 

            Beginning at the locus coeruleus at the top of the brain stem, a stress response is precipitated as norepinephrine is released, affecting the chemical balance (usually excitatory) in all the brain structures involved in the limbic system. The SAM response originates in the lateral hypothalamus as it initiates the release of epinephrine by the adrenal gland. The periventricular nucleus of the hypothalamus releases hormonal neurotransmitters that initiate release of corticotrophin-releasing hormone (CRH) and arginine vasopressin. The pituitary is then stimulated by these hormones to release adrenocorticotropic hormone (ACTH) which then stimulates release of glucocorticoids (i.e., cortisol) by the adrenal cortex. 

Hippocampus, Amygdala, Stress, and Memory Formation

            The hippocampal formation (i.e., subicular complex, hippocampus, and dentate gyrus) plays a significant role in memory formation by converting short-term memory to long-term memory. This involves a process in which the hippocampal formation links perceptions and also links memories of perceptions, helping us to see relationships among stimuli, context, and events. The hippocampus receives information, processes it, and communicates with regions in which memories are stored in a process of consolidating and linking.

            Neurotransmitters are responsible for modulation of the hippocampal activities. The hippocampal formation receives serotonergic input from the raphe nuclei, noradrenergic input from the locus coeruleus, dopaminergic input from the ventral tegmental area, and acetylcholinergic input from the medial septum (Carlson, 2003). Neurotransmitter levels are altered during periods of acute stress, with research showing that even brief periods of stress can result in significant alteration in brain functioning. However, chronic stress has even more impact on neurotransmitter function as dopamine, norepinephrine, and serotonin levels are depleted, having an effect on hippocampal function. Prolonged stress can also result in hippocampal shrinkage and impairment in function (i.e., memory) with studies reporting up to 20% reduction in structure (Sapolsky, 2003).

            Cortisol released in the stress response impairs long-term potentiation in the hippocampus and can prevent memory consolidation. A different process occurs in the amygdala as long-term potentiation of implicit memory is enhanced is the process. This results in memory storage outside conscious awareness and subsequent anxiety resulting when recall occurs outside awareness. The amygdala will later be activated when a preconscious memory is recognized. The sympathetic nervous system will then be stimulated to release CRH, epinephrine, and cortisol, and a chronic stress cycle will result.

Explicit and Implicit Memory

            Neurochemical and psychological processes involved in memory formation vary depending on type, content, and method involved in memory formation. Explicit and implicit memory is further divided dependent on conscious or unconscious involvement and negative or neutral emotional responsivity. Explicit memory is the memory of facts and events and also refers to declarative memories, those which are consciously available for recall and have the ability to be stated (i.e., declared). Implicit memories, also referred to as non-declarative memories, are those which involve perception, stimulus-response, or motor learning that is not conscious. Because implicit memory is outside conscious awareness, an individual is not able to recall or talk about it (Carlson, 2003; Stewart, 2006).        

            In her discussion of memory changes in older adults, Stewart (2006) describes the working memory as a component of explicit memory involved in short-term memory storage. The working memory holds the memory of emotional experiences (i.e., explicit); the implicit memory holds emotional memories. The combination of these two types of memory holds the individual’s conscious experience of an event. The neural system involved in explicit memory includes the hippocampus, amygdala, and other brain regions and depends on encoded cues and evaluation of importance. The emotional element of the experience adds to the hippocampal-amygdalar interaction, enhances memory formation, and results in long-term potentiation. 

Brain Structure and Function in Memory Formation

            Brain structures included in the limbic system are the hypothalamus, amygdala, hippocampus, septum, cingulate gyrus, cortices, tegmentum, fornix, mammillary bodies, forebrain, thalamus, and nucleus accumbens. The hippocampus and amygdala work closely together in enhancing memory storage. The amygdala facilitates the effects of emotion on memory storage, and the hippocampus encodes the memory. Brain structures interact with one another, and no one region is responsible for memory formation and retention. However, structures in the limbic system hold particular relevance. Brain injury and developmental dysfunction show the interrelationship of brain regions and their involvement in emotional experience, conscious recall, and ability to communicate a memory. 

            Hippocampus.  The hippocampus is responsible for recognizing new information, recognizing and assigning significance, and retrieving information in context. Through connections with the rhinal cortex, the hippocampus receives information from the amygdala and the parahippocampal cortex. It receives environmental representations from the prefrontal cortex and integrates them with information from the amygdala. The hippocampus connects with other brain regions, such as the thalamus, septum, and mammillary bodies, and causes an excitatory or inhibitory effect. It communicates with the cortex where associative memories are maintained and is involved in attention, learning, and discrimination. Findings show that the hippocampus is responsible for long-term declarative memory, spatial memory for places, contextual representation of memory, internal representation of motion, and fear response (Stewart, 2006).

            Amygdala. The amygdala is crucial to memory, emotion, and motivation. It has a significant role in attending to relevant sensory input and computing the emotional importance of the stimuli. Because of is relationship to emotion, it is viewed as critical to social and emotional functioning. The amygdala influences the hippocampus in consolidation of memories and exerts either an inhibitory or excitatory influence on the hypothalamus through the stria terminalis. It has connections with the cingulate gyrus and orbital frontal lobe and receives input from the olfactory bulbs and thalamus. It sends information to the hypothalamus, septum, thalamus, and prefrontal cortex. The amygdala interacts with the hippocampus and influences attention, assessment of motivation and social-emotional significance of events, image representation (e.g., facial expressions), learning, and memory formation (Stewart, 2006). 

            Hypothalamus. The hypothalamus provides the interface between the forebrain and the primitive brain and mediates emotional response. It links to the amygdala through the stria terminalis and connects to the hippocampus through the fornix and mammillary bodies. The hypothalamus receives input from the cingulate, parahippocampal gyri, and prefrontal cortex. It facilitates behavioral consciousness and links the autonomic, limbic, and endocrine systems. 

            Prefrontal cortex. The prefrontal cortex is responsible for governing movement, for short term sensory memory, behavioral control, and inhibition of response. It uses declarative memory to modulate contextual response based on impressions and interpretation of cues in the environment. The prefrontal cortex uses information from the amygdala and thalamus and provides input to the amygdala and the hypothalamus regarding emotion. 

            Thalamus. The thalamus communicates directly with the almost every area of the cerebral cortex, projecting almost all sensory information there. The thalamus is responsible for sorting information received from the senses and relaying it to other brain structures in a bi-directional communication pattern.  

            Nucleus accumbens. The nucleus accumbens is the interface between limbic and motor systems. It is connected to the ventral tegmental area, and dopaminergic input from the prefrontal cortex determines motive for behavior. In its involvement in moderating response based on motivational factors, it utilizes both dopamine and acetylcholine.

            Other involved brain structures. The caudate nucleus is involved with the prefrontal cortex in determining behavior. Norepinephrine released by the locus coeruleus stimulates the amygdala, hippocampus, septum, thalamus, and hypothalamus to pay attention. It appears to be responsible for spontaneity, creative thinking, and strategy development (Stewart, 2006).      

Focus of Attention

            Both positive and negative moods affect attention. Recall is based on the state of negative emotional aroused, and negative emotional arousal is dependent on individual coping skills. If individuals can view emotions from a detached perspective, they can engage with alert curiosity and have greater recall. Individuals instructed to suppress negative emotion remember less when tested for memory recall. These results are mediated by the level of negative emotion elicited. A benefit of negative emotion is that individuals learn from the process as they attend to and engage with their negative emotions (Zautra, 2003).

Effect of Mechanism on Immune System

            The field of psychoneuroimmunology studies the interactive effects between emotions and the immune system. Studies have shown that negative emotions hinder immune function, and that emotional dysregulation interrupts the capacity to maintain physical health. The health of an individual’s brain and emotions affects his ability to fight off infection and disease, and both thoughts and emotions have the power to change an individual’s biochemistry and cellular function. Kiecott-Glaser, McGuire, Robles, and Glaser (2002) conducted a literature review of immune system alterations related to health and found psychological contributing factors (e.g., stress, mood states, social support, personality variables, and coping styles). The immune system has a bi-directional communication system with the mind interpreting an event, the body responding, the brain communicating to the immune system via neurochemistry, and the immune system responding by raising or reducing immune system function. The immune system’s response is compromised by stress, anger, anxiety, depression, and other negative emotion states.

            Natural killer (NK) cells are a type of lymphocyte whose responsibility is the elimination of infection from the body. These NK cells recognize and eliminate both invader cells from the outside and natural cells that are malignant. However, NK cells are suppressed by stress. When negative emotion occurs, levels of NK cells are reduced. NK cells maintain the body’s health by eradicating threats. Individuals with low NK activity are prone to infection and disease.

            The stress response is a cascade of reactions in the body that results in a series of chemicals being released as the body attempts to restabilize the system. The adrenal glands secrete epinephrine and cortisol. The pituitary gland releases ACTH. Neurotransmitters such as CRH, epinephrine, serotonin, dopamine, and norepinephrine are released by involved brain structures (e.g., limbic system, amygdala, cortex, hippocampus, and locus coeruleus). The body’s energy reserves become exhausted if the stress continues, and essential neurotransmitters, such as dopamine, norepinephrine, and serotonin, are depleted.

            NK cells are put at risk during this process. The active hormones - CRH, ACTH, and cortisol – all interact with T-cells and NK cells, epinephrine, other hormones and neurotransmitters, neuromodulators, and genes. Together these alter the body’s immune function and depress NK cell activity. Cortisol depresses the immune system, having an effect on the number and effectiveness of lymphocytes in the body by preventing new T-cells from being formed, redistributing immune cells, and sometimes destroys them (Sapolsky, 1994). This depression of NK cell activity leaves the body susceptible to infection and disease. 

Application of Findings 

            Memory in trauma. Client memory may be severely disrupted when significant trauma has occurred. Understanding of the process underlying memory loss is crucial to working with this client group. Explicit memory has not been encoded; however, implicit memory holds event recall, and therapeutic strategies may include modalities that affect implicit memory.  

            Dissociation. Dissociation during trauma and ongoing as a coping skill is common in clients who have trauma histories. However, the view of dissociation as responsible for loss of memory is not supported by research. Dissociation as a coping strategy preserves individual ego strength in the face of threat or damage too great to face in that moment. However, a more lucrative conversation can occur with clients as the ongoing benefit of dissociation is explored.

            Declarative versus non-declarative. Trauma memories are not always held in declarative memory due to high negative emotional content. Finding avenues to non-declarative memory appears a worthwhile therapeutic endeavor.

            Treatment ramifications.  Treatment strategies that access implicit memory are predicted to be successful in resolution of trauma symptoms. Examples include sensorimotor therapy, somatic experiencing, hypnosis, meditation, yoga, and other body work.

References

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Abercrombie, H. C., Kalin, N. H., Thurow, M. E., Rosenkranz, M. A., & et al. (2003). Cortisol variation in humans affects memory for emotionally laden and neutral information. Behavioral Neuroscience, 117(3), 505. Retrieved May 29, 2006, from Proquest.

Abercrombie, H. C., Speck, N. S., & Monticelli, R. M. (2006). Endogenous cortisol elevations are related to memory facilitation only in individuals who are emotionally aroused. Psychoneuroendocrinology, 31, 187-196.

Cahill, L., Babinsky, R., Markowitsch, H. J., & McGaugh, J. L. (1995). The amygdala and emotional memory. Nature, 377(6547), 295-296.

Carlson, N. R. (2003). Physiology of behavior (8th ed.). Boston: Allyn & Bacon.

Kiecott-Glaser, J. K., McGuire, L., Robles, T. F., & Glaser, R. (2002). Psychoneuroimmunology: Psychological influences on immune function and health. Journal of Consulting Clinical Psychology, 70(3), 537-547.

LeDoux, J. R. (1996). The emotional brain. New York: Simon & Schuster.

McPherson, F. (2006). About memory. Retrieved May 19, 2006, from http://www.memory-key.com/NatureofMemory/emotion.htm.

Sapolsky, R. (2003). Taming stress. Scientific American, 289(3), 87-96.

Sapolsky, R. M. (1994). Why zebras don't get ulcers. New York: W.H. Freeman.

Southwick, S. M., Davis, M., Horner, B., Cahill, L., Morgan, C. A., Gold, P. E., et al. (2002). Relationship of enhanced norepinephrine activity during memory consolidation to enhanced long-term memory in humans. The American Journal of Psychiatry, 159(8), 1420-1422.

Stewart, S. E. (2006). Personality correlates to memory change in older adults. Retrieved May 19, 2006, from http://web.uccs.edu/sstewart/Introduction.htm.

Zautra, A. J. (2003). Emotions, stress, and health. New York: Oxford.