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How the Right Kind of Stress Can Improve Your Brain Power

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How the Right Kind of Stress Can Improve Your Brain Power

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"It turns out that the right kind of stress, in the right amounts, for the right amount of time have been shown to help improve symptoms of every single condition mentioned above."

Source: Article
Author: Steven Baldridge
Value: offers another perspective on stress, demonstrates the helpful attributes of stress, explains how different types of stress can be good or bad

https://www.uhhospitals.org/Healthy-at-UH/articles/2019/08/how-stress-can-improve-your-brain-power

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The Mind and Mental Health: How Stress Affects the Brain

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The Mind and Mental Health: How Stress Affects the Brain

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"But when chronic stress is experienced, the body makes more cortisol than it has a chance to release. This is when cortisol and stress can lead to trouble. High levels of cortisol can wear down the brain’s ability to function properly."

Source: Article
Author: Rebecca Bernstein
Value: discusses multiple studies pertaining to stress, explains the leading causes of stress, describes short-term and long-term impacts of stress

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Stress continues to be a major American health issue, according to the American Psychological Association. More than one-third of adults report that their stress increased over the past year. Twenty-four percent of adults report experiencing extreme stress, up from 18 percent the year before.

It's well-known that stress can be a detriment to overall health. But can stress actually change the physiology of the brain? Science says yes.

Defining Stress

The National Institute of Mental Health defines stress as simply "the brain's response to any demand." Given that definition, not all stress is bad. It is simply a response. How harmful it ultimately depends on its intensity, duration and treatment.

Stress takes a variety of forms. Some stress happens as the result of a single, short-term event - having an argument with a loved one, for example. Other stress happens due to recurring conditions, such as managing a long-term illness or a demanding job. When recurring conditions cause stress that is both intense and sustained over a long period of time, it can be referred to as "chronic" or "toxic" stress. While all stress triggers physiological reactions, chronic stress is specifically problematic because of the significant harm it can do to the functioning of the body and the brain.

Leading Causes of Stress

Stress occurs for a number of reasons. The 2015 Stress in America survey reported that money and work were the top two sources of stress for adults in the United States for the eighth year in a row. Other common contributors included family responsibilities, personal health concerns, health problems affecting the family and the economy.

The study found that women consistently struggle with more stress than men. Millennials and Generation Xers deal with more stress than baby boomers. And those who face discrimination based on characteristics such as race, disability status or LGBT identification struggle with more stress than their counterparts who do not regularly encounter such societal biases.

Physiological Effects of Stress on the Brain

Stress is a chain reaction. "When someone experiences a stressful event, the amygdala, an area of the brain that contributes to emotional processing, sends a distress signal to the hypothalamus," Harvard Health Publications of Harvard Medical School explains. "This area of the brain functions like a command center, communicating with the rest of the body through the nervous system so that the person has the energy to fight or flee."

This "fight-or-flight" response is responsible for the outward physical reactions most people associate with stress including increased heart rate, heightened senses, a deeper intake of oxygen and the rush of adrenaline. Finally, a hormone called cortisol is released, which helps to restore the energy lost in the response. When the stressful event is over, cortisol levels fall and the body returns to stasis.

Effects of Chronic Stress on the Brain

While stress itself is not necessarily problematic, the buildup of cortisol in the brain can have long-term effects. Thus, chronic stress can lead to health problems.

Cortisol's functions are part of the natural process of the body. In moderation, the hormone is perfectly normal and healthy. Its functions are multiple, explains the Dartmouth Undergraduate Journal of Science. In addition to restoring balance to the body after a stress event, cortisol helps regulate blood sugar levels in cells and has utilitarian value in the hippocampus, where memories are stored and processed.

But when chronic stress is experienced, the body makes more cortisol than it has a chance to release. This is when cortisol and stress can lead to trouble. High levels of cortisol can wear down the brain's ability to function properly. According to several studies, chronic stress impairs brain function in multiple ways. It can disrupt synapse regulation, resulting in the loss of sociability and the avoidance of interactions with others. Stress can kill brain cells and even reduce the size of the brain. Chronic stress has a shrinking effect on the prefrontal cortex, the area of the brain responsible for memory and learning.

While stress can shrink the prefrontal cortex, it can increase the size of the amygdala, which can make the brain more receptive to stress. "Cortisol is believed to create a domino effect that hard-wires pathways between the hippocampus and amygdala in a way that might create a vicious cycle by creating a brain that becomes predisposed to be in a constant state of fight-or-flight," Christopher Bergland writes in Psychology Today.

Effects of Stress on the Body

Chronic stress doesn't just lead to impaired cognitive function. It can also lead to other significant problems, such as increased risk of heart disease, high blood pressure and diabetes. Other systems of the body stop working properly too, including the digestive, excretory and reproductive structures. Toxic stress can impair the body's immune system and exacerbate any already existing illnesses.

Explore Health Science Degrees

Plasticity and the Brain: The Body's Recovery System

Plasticity, or neuroplasticity, refers to the ways that neural pathways are able to re-form in the brain. It's true that these pathways - like the one between the hippocampus and the amygdala - can get severely damaged due to constant exposure to stress, but such changes are not necessarily permanent. While stress can negatively affect the brain, the brain and body can recover.

Young adults, especially, are able to recover from the effects of stress, according to Proceedings of the National Academy of Sciences ( PNAS). Age has a direct correlation with the reversibility of stress-related damage. It's much more difficult for older adults to regain or create new neural pathways than their younger counterparts.

That's not to say all hope is lost for older adults. PNAS points out that "interventions," or activities that combat stress' wear-and-tear on the brain, are effective regardless of age. Interventions including activities like exercising regularly, socializing and finding purpose in life enable plasticity.

It can seem like stress is an inevitable part of life, but chronic stress can have real and significant consequences on the brain. Understanding these effects and how to combat them can help promote overall health.

Understanding How Stress Affects the Brain

Professionals working in health and human services or psychology have the opportunity to help others manage their stress effectively and understand how stress affects the brain. Touro University Worldwide offers a variety of fully online degree programs at the bachelor's, master's and doctoral level that prepare students for careers in these fields.

# data[].attributes.attachment_link.title
The Mind and Mental Health: How Stress Affects the Brain

# data[].attributes.attachment_link.description
Stress continues to be a major American health issue, according to the American Psychological Association. More than one-third of adults report that their stress increased over the past year. Twenty-four percent of adults report experiencing extreme stress, up from 18 percent the year before. It's well-known that stress can be a detriment to overall health.

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2009: Airplane crash-lands into Hudson River; all aboard reported safe

# data[].attributes.subject
2009: Airplane crash-lands into Hudson River; all aboard reported safe

# data[].attributes.body
""It would appear that the pilot did a masterful job of landing the plane in the river and then making sure that everybody got out," Bloomberg said."

Source: Case Study
Person of Interest: Chesley B. Sullenberger
Value: explains the functional capacity of the brain under stress in real time, shows an example of increased brain function under extreme stress

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2009: airplane crash-lands into hudson river; all aboard reported safe - cnn

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2009: Airplane crash-lands into Hudson River; all aboard reported safe

# data[].attributes.attachment_link.description
CNN archive news report: A US Airways plane with 155 people on board ditched into a chilly Hudson River on Thursday, apparently after striking at least one bird upon takeoff from New York's LaGuardia Airport, according to officials and passengers.

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"Furthermore, compared to people with average cortisol levels, those with high cortisol levels had worse visual perception, memory, and global cognitive function."

Source: Study and Article
Author: Yuko Hara
Value: describes a comprehensive study, suggests ways to avoid stress, explains specific cranial structures and how they're impacted by stress

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Prolonged stress is often associated with health problems, such as heart disease, anxiety disorders, and sleep problems. A recent study published in Neurology reported that higher blood levels of the stress hormone cortisol are also associated with memory impairments and smaller brain volumes in young and middle-aged adults [1]. This relationship was especially pronounced in women compared to men.

These findings come from a large study of 2,231 men and women (average age, 48.5 years old) who were free of dementia. Their blood cortisol levels were measured, and then cognitive functions were evaluated, including memory, abstract reasoning, visual perception, attention, and executive function. Brain MRI imaging was also carried out in most of the participants (2,018 people) and total brain volume, brain volumes of different brain regions, and structural changes in the brain were assessed.

After adjusting for many variables, people with high blood cortisol levels (in the highest third) had smaller total cerebral brain volume compared to people who had average levels (in the middle third). Interestingly, this association was present in women but not among men, though the reason for this sex difference is unknown. Furthermore, compared to people with average cortisol levels, those with high cortisol levels had worse visual perception, memory, and global cognitive function. These associations between high cortisol levels and worse cognitive functions were found in both men and women.

These results are largely consistent with findings from previous studies, though most prior studies had focused on the relationship between cortisol levels and sizes of the hippocampus, a brain region important for memory functions [2][3]. The current study found that the associations between cortisol levels and brain structure are not specific to the hippocampus but occur throughout the brain.

While this study was strong in terms of its large size, extensive brain imaging data, and adjustment for potential variables that could confound the data, there were some limitations. Cortisol levels were measured only at a single time point so it is not known if this measure represents the individual's average cortisol level across time. Also, because this study was an observational study, it was not designed to prove that high cortisol levels cause brain shrinkage or cognitive decline. It is worth noting that there is a clinical trial currently underway that is testing whether a drug that inhibits the actions of cortisol can effectively treat people with mild Alzheimer's disease [4]. This study is scheduled to be completed in the summer of 2019.

If you have high stress levels, protect your brain by making changes to your lifestyle and learning ways to cope. The Centers for Disease Control and Prevention offers tips to reduce stress, such as eating healthy, exercising, and getting enough sleep.

1. Echouffo-Tcheugui JB, Conner SC, Himali JJ et al. (2018) Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology 91, e1961-e1970.

2. Knoops AJ, Gerritsen L, van der Graaf Y et al. (2010) Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study. Biol Psychiatry 67, 1191-1198.

3. Lupien SJ, de Leon M, de Santi S et al. (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1, 69-73.

4. Ruffles V (2016) A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu) (XanADu). ClinicalTrials.gov.

Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.
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# data[].attributes.attachment_link.description
Prolonged stress is often associated with health problems, such as heart disease, anxiety disorders, and sleep problems. A recent study published in Neurology reported that higher blood levels of the stress hormone cortisol are also associated with memory impairments and smaller brain volumes in young and middle-aged adults [1].

# data[].attributes.body
"Exposure to high or very high stress acutely chronically impairs the formation of explicit memories and, more generally, of those that require complex, flexible reasoning while improving performance of implicit memory and well-rehearsed tasks ."

Source: Study
Author: Carmen Sandi
Value: describes specific mental processes (eg memory), provides cohesive models and charts, tests varying levels of stress

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Stress and Cognition: Psychological Basis and Support Resources

# data[].attributes.subject
Stress and Cognition: Psychological Basis and Support Resources

# data[].attributes.body
"This impairment translates into behavioral changes, loss of memory, inability for decision-making, and attention problems."

Source: Book Chapter
Author: Tamara Cibrian-Llanderal, Montserrat Melgarejo-Gutierrez, and Daniel Hernandez-Baltazar
Value: describes causes of stress, explains cellular processes with regards to stress, suggests possible methods of improving the impacts of stress on cognitive function

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Open access peer-reviewed chapter

DOI: 10.5772/intechopen.72566

Abstract

Executive functions are processes that help in tasks such as reasoning, planning, troubleshooting, and management of the individual's own life. A consequence of the specific connections of stress is that executive functions tend to be interrupted when the stimulation load is so big that the individual becomes stressed. The level of cellular stress becomes evident with the increase of cortisol. Cellular processes such as inflammation, proliferation/death, and oxidative stress have been shown in murine models resembling cognitive impairment in humans. This impairment translates into behavioral changes, loss of memory, inability for decision-making, and attention problems. The incorporation of factors, such as drug use and bullying, promotes the impairment of executive functions. Resorting to strategies, such as exercising, environmental enrichment, and changes in the diet, constitutes an excellent aid in the promotion of academic achievement. In this chapter, we discuss the impact of stress on cognitive executive functions associated with academic achievement and also suggest strategies to reduce the impact of stressing factors.

Keywords

academic achievement

cognition

executive functions

psychosocial stressor

physiological stressor

chapter and author info

Authors

Tamara Cibrian-Llanderal*

CONACYT - Instituto de Neuroetologia, Universidad Veracruzana, Mexico

Montserrat Melgarejo-Gutierrez

Facultad de Medicina, Universidad Veracruzana, Mexico

Daniel Hernandez-Baltazar

CONACYT - Instituto de Neuroetologia, Universidad Veracruzana, Mexico

*Address all correspondence to: tamaracibrian@gmail.com

DOI: 10.5772/intechopen.72566

From the Edited Volume

Health and Academic Achievement

Edited by Blandina Bernal-Morales

1. Introduction

Stress is a biological response to internal or external demands which have an impact on cellular homeostasis. The frequency and intensity of the stressful stimuli can promote physiological and psychological effects on the body, such as the executive functions of the brain. Executive functions are a set of cognitive skills that allow for the anticipation and establishment of goals, the design of plans and programs, the initiation of the activities and the mental operations, self-regulation, and task monitoring. The prefrontal cortex acts as a controller of executive functions. The executive functions, which help us to organize thoughts, tend to be interrupted when the stressors load is too high [ 1].

The study of the determinants of academic performance has attracted a remarkable interest in the last few years, given the need to investigate new variables that explain frequent school failure and discouragement in students. Predicting the effect of executive functions on academic performance is important for adequate adaptation of the individual to the specific requirements of the school context. The association between chronic or acute stress and academic performance might be mediated by the effects of cortisol in the prefrontal cortex, which promotes impairment in cognitive functions. Prolonged exposure to stress during different stages of development interferes with both academic achievement and executive functions that provide a basis for learning [ 2, 3].

Several studies conducted both in animal and human models indicate that factors, such as physical activity, sleep, and a healthy diet, promote optimal cognitive functioning and better academic performance. In this chapter, we discuss both the impact of psychosocial and physiological stressors on executive functions associated with academic performance and some strategies that reduce the impact of stressors. This manuscript compiles a comprehensive review of articles and books indexed in PubMed, SciELO, Scopus, and Google Advanced Scholar.

2. Stress

2.1. Neuroendocrine response

The term "stress" was coined by Hans Selye in 1936 and is defined as a non-specific response of the organism in the presence of any demand imposed. It is produced by the alteration of the cellular homeostasis, with physiological and psychological consequences in the body [ 1]. At molecular level, stressors can generate the activation of oxidative stress, which is explained by the imbalance of reactive oxygen species such as O 2, O ₂−, OH −, H ₂O ₂, and the antioxidant molecules (vitamin C, E, flavonoids) [ 4]. Stress at cellular level is always present to facilitate the processes of cell proliferation, maintenance, and death [ 5].

At behavioral level, it is recognized that stressors are a threat to which the body requires adaptive adjustments that will allow it to maintain homeostasis and ensure the survival based on experience, biological predisposition, and the status of the organism [ 6]. During stress, three phases have been distinguished: (1) alarm, (2) resistance, and (3) exhaustion phase. In the alarm phase, the initial reaction of the body to a stimulus generating stress, which restores homeostasis; in this phase, the stressor promotes the stimulation of hypothalamus to secrete ACTH-releasing hormone (CRH). In the resistance phase, prolonged exposure to the stressor leads the exit of the stressful condition or adaptation. During the exhaustion phase, the gradual reduction of the stress response leads to the gradual loss of adaptive capacities [ 7].

The physical and psychological stressors can trigger the activation of neuronal circuits and peripheral process, for example the inflammation. Cytokines produced by the cells of the immune system can exercise their anti- or pro-inflammatory effect on the cells of the CNS and peripheral organs [ 8]. The IL-1, IL-6, and IL-17 act on the HPA axis by increasing the secretion of ACTH and cortisol [ 9]. The TNF-alpha has the ability to destroy certain cell lines and initiates the cascade of proinflammatory cytokines [ 10]. The regulatory suppressive function of the immune response will depend on the balance of the synthesis of cytokines. If the inflammation is prolonged, other systems will also be activated such as the endocrine system and neurotransmission systems (e.g. noradrenergic, serotonergic, and dopaminergic) [ 11] ( Figure 1).

Studies in humans and in experimental animals have shown that psychological stressor can suppress or increase the immune response, depending on the length of the stress (acute or chronic). Both in acute and chronic stress, physical exercise induces increase in the production of IL6, IL-4, IL-10, IL-13, IL-17, and TNFα [ 12]. However, few studies have explored the variation of cytokines in individuals with physical activity; in the case of the IL-17, it has been determined that their serum levels are not altered by the effect of practicing vigorous physical activity (chronic stress) [ 13]. The real impact of stressor is associated with intensity and frequency.

2.2. Stress and cerebral cortex

The prefrontal cortex allows efficient connectivity between the circuits associated with emotions, memory, and planning. An example of this is the intricate relationship with neurons of the locus coeruleus, substantia nigra pars compacta, and ventral tegmental area, by neuromodulators such as norepinephrine and dopamine. Despite to neuroanatomical location and catecholaminergic nature of its afferents, the prefrontal cortex is highly sensitive to damage; for example, during acute stress in rats, the neurites change shape and length over several weeks post damage [ 7, 14]. In preclinical studies in rats, two sensors and/or regulators of stress associated with the prefrontal cortex have been identified. (1) The direct connection with the amygdala provides an important point of regulation. In the presence of stressful conditions, the prefrontal cortex becomes highly sensitive to damage due to the catecholaminergic nature of its innervating afferents. (2) The critical point of regulation of the amygdala to the prefrontal cortex is characterized by the promotion of the release of noradrenaline and dopamine, which will act at the level of different receptors (D1, D2, A1, β1), activation of hydrogen, calcium, and nitrogen bombs (HCN channels), and even as triggers of the release of neurotrophic factors such as BDNF and GDNF ( Figure 2). In addition, the endocannabinoid-mediated pathway also acts as a regulator of stress and emotions [ 15].

Human studies have revealed that the "self-control of stress" can promote reduction of the action of the amygdala, and the subject can solve the stressful situation. An opposite situation will lead deleterious effect on mental and physical health. It has been determined that the absence of control of stress can promote the acquisition of addictive behaviors. During adolescence, addiction to nicotine [ 16], or even to the internet [ 17], causes cortical alterations due to decreased mesolimbic dopaminergic function [ 18]. Limited studies that have focused on this topic have opened a new line of study. Interestingly, the incidence of stressors can promote the establishment of three levels of response to stress in humans: (1) mesencephalic nuclei, (2) cellular response, and (3) systemic (immune-endocrine) [ 19]. This leads us to infer that: a lack of control strategies can promote alterations at these three levels, increasing the levels of cortisol in the blood, which has an impact on the psychomotor integrity of the individual. At present, diverse activities are being suggested to manage the impact of academic stressors, such as arts-based activities [ 20] or controlled physical activities [ 21].

3. Executive functions

Executive functions are a set of cognitive skills that allow for anticipation and establishment of goals, the design of plans and programs, the initiation of activities and mental operations, self-regulation, task monitoring, the precise selection of behavioral, flexibility for cognitive tasks, and organization in time and space. On the other hand, various authors have defined cognitive control as an "executive control" which refers to a set of higher order processes that modulate the interactions of the environmental context of the subject [ 22, 23]. These functions aim to optimize the selection, management, and coordination that underlie aspects such as perception, memory, and execution [ 24].

According to Diamond [ 25], the key executive functions are inhibitory control, working memory, and cognitive flexibility. Other functions, such as reasoning, planning, and organization, would be built from the three main functions. Other authors have defined the executive functions using warm and cold. Warm executive functions are cognitive/emotional processes related to decision-making, motivation, and social cognition. Cold executive functions are related to the rational/cognitive process of high order skills that are used when emotions are not an important factor [ 26].

Executive functions can be assessed using neuropsychological tests and are dependent on the prefrontal cortex. The frontal lobes plan, regulate, and control human behavior. This control allows the individual to evaluate and select the most appropriate response and avoid impulsive responses, restraining compulsive behavior, and appetitive behavior. At neural level, the prefrontal cortex, particularly the dorsolateral portion, is a fundamental region involved in executive functions. Other regions, such as the orbitofrontal cortex portion, are closely related to the limbic system. The thalamus and the basal ganglia are brain regions also involved in executive functions [ 27].

3.1. Executive functions and academic performance

When a child enters school, he/she is in need of a series of cognitive processes (comparison, attention, differentiation) to be able to develop reading and writing and mathematical calculation, that is why, a proper neurological maturation is essential to deal successfully with the demands of learning, as the alteration of cognitive processes translates into learning problems [ 28].

The predictive effect of executive functions on academic performance is important for the proper adaptation of the individual to the specific requirements of a learning context; the correct development of the executive processes makes it possible for the individual to recognize and represent mentally different problematic situations, in addition to designing strategies for the resolution of them. There have been some works that have focused on evaluating executive function and academic performance.

A study was conducted in which the relationship between performance in mathematics and the performance in tasks of working memory and processing speed was assessed, finding that children with normal performance in the area of mathematics were faster and had greater accuracy in responding to tasks that required numerical identification, recovery and retention of numerical information, and ability to do mathematical calculations in relation to children with poor performance. In error-detection tasks, both groups of children (low performance and normal performance) could recognize the errors without difficulty. However, children with poor performance failed in the detection of such errors at a rate of 1 of 3 tests [ 29]; one of the explanations of the authors is that there is an inappropriate intervention of the central executive that regulates cognitive processes such as the transmission of information to long-term memory, planning, and recovery strategies.

Blair and Razza [ 30] conducted a longitudinal study in which they measured the capabilities of the temperamental factor associated with self-control (Effortful Control), understanding of false belief, inhibitory control, and shift of attention. The objective was to study the relationship between some skills involved in executive functions and academic performance in mathematics and language. The results showed that the scores of children at the initial level, in shift of attention and inhibitory control, did not predict performance in the tasks of phonological and letter recognition. However, the scores on inhibitory control were related with the performance at the mathematical tasks during pre-school period (3-5 years). During this period, the scores of inhibitory control and attention shift were associated with the literary capacity of children (phonetic recognition and knowledge of letters).

A longitudinal study in children from 5 to 7 years evaluated the way in which short-term memory, working memory, inhibitory control, cognitive flexibility, and planning impacted on academic performance. The results showed that performance on tasks of short-term memory and working memory was associated with better initial performance of children in reading and math skills. Likewise, analyses of correlation and regression carried out revealed that the visuospatial memory and working memory operated as predictors of children's mathematical performance in all the periods in which they were evaluated. On the other hand, inhibitory control, flexibility, and planning acted as predictors of general learning capacity, but were not associated with the performance of any specific domain [ 31].

Reyes and colleagues [ 32] found that the correlation between the variables identified significant relationships between academic performance and executive functions. At the age of 6, significant correlations are found between selective sustained attention and working memory with all the courses understanding that these courses require the constant ability to select the most important information and focus attention for long periods of time within the classroom, mainly in the areas of Math, English, and Social Sciences; considering that the children of 4-6 years have short periods of sustained attention in the presentation of a task, from 6 years, the attention that children can give to a task or to a game can be extended for a long time.

In summary, the different studies mentioned show that a good academic achievement is predictive of the executive capacity that individuals have, this must be considered to promote strategies for improvement in the executive functions of the students through training to have impact in academic performance.

3.2. Stress and executive functions

One of the factors that can affect executive functions is stress. As we mentioned earlier, stress occurs when demand exceeds the regulatory capacity of the organism. It is very difficult to determine the extent of the impact and the duration of daily stress, especially if in acute stress situations where the individual is facing situations with a physical or psychological stimulation in which he/she must decide quickly or make an assessment of a particular situation. Stressors promote physiological, psychological, and behavioral reactions, but individuals react differently to stressors. That makes a laboratory setting very useful for the study of the psychophysiological responses to stressors of different nature, which allow evaluate subjects under controlled modulatory variables [ 33].

There is evidence of the negative effect of high levels of circulating of stress-induced glucocorticoids on cognitive performance [ 2, 34]. The different studies related to declarative memory tasks have focused on the hippocampus [ 35, 36]; some other studies have examined the effect of stress on working memory [ 37], which has shown that the administration of cortisol can also adversely affect the performance of the working memory [ 35, 38]. Some authors have evaluated one or two components of the executive functions under conditions of stress where they have observed that stress can reduce attention in inhibition [ 39, 40]; the administration of tasks assessed with paradigms of dual task was improved under stressful conditions [ 41], while the administration of tasks through a paradigm change of tasks was observed to be impaired under conditions of stress [ 42]. A systematic study investigated the effect of stress in five components of the executive functions: attention and inhibition, task management, planning, monitoring, and coding. The results showed that stressed participants had a better performance compared with non-stressed participants in all the components with the exception of the monitoring [ 43]. One study evaluated the relationship between specific stressors and deficits in executive functions in undergraduate students. The results determined that general social abuse was the factor most correlated with deficits in executive function. Factors such as challenges of development (struggle and dissatisfaction with cognitive and physical attributes and abilities) and dissatisfaction with school were also predictive of diminished executive functions [ 44].

Chronic stress can generate high levels of cortisol in the prefrontal cortex, which can lead to an impairment of cognitive functions. There is evidence that stressors such as bullying and addiction can affect the executive functions; although they are not the only existing stressors, they are to be found with higher prevalence in the school setting.

Questions about how stress can affect or improve behavior are important in different contexts and in this particular case on academic performance. One of the factors that interfere suggests that the controllability is a key factor on the impact of stress on behavior; to learn how to control stress-causing factors protects people from the negative effects of stress in tasks of high cognitive demand. In addition, research suggests that the impact of stress on cognitive functioning depends on an individual's response to stressors: moderate responses to stress can lead to improved performance, while extreme responses (high or low) can lead to a low performance [ 45, 46, 47].

Factors such as bullying and addictions stimulate stress by promoting specific neurophysiological responses, followed by alterations in executive functions. Components such as physical activity, good nutrition, and sleep hygiene can reduce academic stress and its neurophysiological consequences ( Figure 3).

3.3. Bullying

Bullying is characterized by intentional, repetitive, and persistently aggressive behavior causing harm to a victim [ 48]. Several studies have investigated the social and emotional aspects related to bullying; however, few studies evaluate how cognitive aspects are involved. Studies with aggressive individuals indicate a malfunction in cognitive functioning and decision-making. One study found that children who were not involved in bullying situations such as bullies or victims had better scores on intelligence tests. Both victims and bullies had greater difficulties in the inhibitory control according to the reports given by the parent version of the Behavior Rating Inventory of Executive Function (BRIEF); the result suggests a probable deficit in executive functioning related to being involved in situations of bullying [ 49].

Medeiros and collaborators evaluated decision-making, inhibitory control, working memory, and cognitive flexibility in children. They found that the bully made less favorable decisions in assessments for decision-making, while the group of victims took more time to complete assessments of cognitive flexibility. This study suggests that bullies have difficulties in warm executive functions, while victims have lower performance in cold executive functions [ 50].

3.4. Addictions

The association between the low academic performance and the use of alcohol (risk consumption) has been studied by several authors in the literature [ 51]. Due to their biological limitations in the ability to engage and integrate executive functioning, teens are very susceptible to the noxious consequences of the use of tobacco, alcohol, and other drugs. Unlike adults, alcohol causes greater impact on the brain of adolescents and young adults in the areas of working memory and learning. The early onset of nicotine use leads to deterioration in memory capacity and increases the frequency of episodes of depression and heart irregularities. Marijuana consumption associated with low academic performance has been described [ 52]. Other drugs, such as stimulants and opioids, are directed to the dopaminergic receptors in the brain and can cause damage throughout life to the development of impulse control and the ability to experience reward. Substance abuse contributes to the delay in skills of the executive functions and in immature or under-controlled emotional responses

4. Strategies for the good academic performance: Physical activity, sleep, and diet

4.1. Physical activity

Several studies conducted on animal and human models provide sufficient evidence for an important relationship between various factors such as physical activity, sleep, and healthy food, with optimal cognitive functioning. This invariably leads to a better academic performance. These studies have been conducted through different stages of development, from prenatal to old age. Some of the cognitive functions that may be affected by the activities or changes throughout life are short-term and long-term memory, learning, attention, spatial memory, and working memory, among others. Evidence suggests that the connection between these cognitive functions, physical activity, nutrition, sleep time, and social interactions have a direct impact on the structure and function of the central nervous system [ 53].

Consequently, cognitive control has been implicated as an important and necessary component of academic performance, in that it relates to brain areas that are involved in processes of behavior and processing of information required to interact with the environment in both children and adults. Neuroimaging studies such as magnetic resonance imaging (MRI) have been used to demonstrate potential mechanisms by which physical activity improves cognitive health. These techniques have demonstrated that physical activity improves the function and structure of the brain [ 53, 54], possibly associated with an increase in the neuroplasticity, and neurogenesis due to BDNF which can be measured peripherally in blood serum or plasma (pBDNF) [ 55]. Therefore, it is possible to analyze a direct correlation between physical activities with neurocognitive changes and subsequent blood analysis directly after the physical activation. BDNF belongs to the most important family of proteins in the brain, which plays an important role in neurogenesis, synaptic plasticity, learning, and memory. Therefore, a low concentration of pBDNF can lead to a poor execution of cognitive tasks associated with spatial memory in the hippocampus [ 56].

Physical activity is defined as bodily movement that requires energy output above normal with physiological demands, which can be measured through records and data obtained by accelerometers or other devices. It has been demonstrated that physical activity can have an indirect effect on the body by reducing stress and with it, the oxidation and inflammation, improving cognitive function, and reduced risk of developing dementia [ 57]. In addition, it has also been observed that a decrease in physical activity coincides with an increase in age. This in turn shows an impact on the functioning of neurotransmitters of the dopaminergic system [ 58], which is important for both processes. The absence of dopamine can anticipate problems with working memory and learning [ 59]. It has also been suggested that there is a relationship between cardiovascular exercise and the volume of gray matter in the hippocampus and prefrontal cortex in the elderly population, which results in an improvement in the memory. Other self-report studies of subjects with memory problems have shown that physical activity over 6 months significantly improves memory compared with those subjects who did not perform physical activity as a control group [ 60].

Recently, a group of researchers conducted a comprehensive analysis of studies done in humans over the past 15 years. The aim of this study was to determine the relationship between various factors, such as age and physical activity, and the performance of cognitive skills and memory. The results showed a strong relationship between cognitive skills and physical activity, which reduced by up to 10% the risk of developing neurodegenerative diseases such as Alzheimer's and dementia. In addition, they also showed that the intensity of exercise impacts differently on the functions and cognitive skills. For example, low-intensity aerobic exercise has a positive effect on visual perception and attention, while moderate physical activity impacts in a general way the cognitive skills such as memory, verbal memory, and attention. The previous, intense exercise requires much more attention and less cognitive processing due to a reduction in reactions, selective attention, and flexibility toward the tasks. Currently, there is controversy about the type of exercise and the greater benefits in the cognitive performance; in this sense, this study suggests that physical activity is without doubt a good factor of cognitive improvement, but more studies are needed on the intensity, type of exercise, and cognitive activity, which deserve to be analyzed in depth and from different scientific points of view [ 61].

In summary, all these studies point to the fact that physical activation at different stages of life is an important factor for the maintenance of a healthy body and, in addition, for mental health and cognitive therapy. In children, physical activity significantly improves selective attention, working memory, and learning diminishing behavioral problems and overweight and improving their academic performance. In adults and the elderly, it prevents the deterioration of memory and improves the execution of tasks, as well as maintenance of optimal mental health through the activation of the dopaminergic system and neurogenesis, which can prevent the development of neurodegenerative diseases [ 62].

4.2. Sleep

Today, reduced and/or disrupted sleep has become common among people of all ages, including pre-school children. The reduction in the hours of sleep in adolescents is considered a public health problem by the American Academy of Pediatrics. These changes can lead to the deterioration of various physiological functions, particularly in the brain, such as learning, memory, and the deterioration of cognitive processes and therefore of academic performance. Sleep is a physiological process controlled and orchestrated by diverse brain areas, including the cortex, brainstem, hypothalamus, thalamus, and hippocampus, and the release of neurotransmitters that in addition to generating the wake-sleep cycle is also involved in the execution of tasks and behaviors on a daily basis [ 63]. It has been suggested that during sleep there is a flow and storage of information between the hippocampus and cerebral cortex; the interaction between these areas promotes the consolidation of information gained during the day, suggests that the storage´s model promote the short-term memory consolidation into hippocampus, and long-term memory on the brain cortex [ 63]. In the first place, it is known that Rapid Eye Movement (REM) sleep and slow-wave sleep (NREM) provide different processes of memory storage, for example, it has been proposed that NREM facilitates declarative memory or explicit memory, while REM facilitates the non-declarative or procedural memory and learning [ 64]. During NREM sleep, the hippocampus consolidates the memory and transfers the information to the cortex for the long term. Stickgold and colleagues suggest that during REM sleep cortical plasticity could be promoted, which plays an important role in procedural memory or in a high-level cognitive processing, but not so in episodic memory bound to a hippocampal process [ 65]. In addition, it is believed that the processes of neuronal plasticity take place both in the NREM [ 66] and in the REM [ 67].

The pace of activity currently has led us to a reduction and alteration of the wake-sleep cycle and with that the presence of many disorders associated with this. It is for this reason that many studies have focused their attention on studying the deleterious effects of deprivation and/or alteration of sleep on different processes of the body as is cognitive deterioration. Currently, sleep deprivation is very common among students, which have been associated with poor academic performance and a decrease in physical activity. For example, numerous investigations have found evidence that sleep in infants plays an important role in the consolidation of memory, making the process more stable and less prone to forgetfulness [ 65]. Another study conducted on infants from 6 to 12 months of age showed that taking naps for at least 30 minutes significantly improves learning and memory in association with objects in comparison with those infants who did not take naps. In addition to the benefits on learning and memory, it has been shown that naps may be beneficial for language learning. It is known that the sleep in adolescents may be affected by the use of electronic devices at night. This directly affects the neurons of the suprachiasmatic nuclei and the pineal gland, inhibiting the secretion of melatonin and delaying or disrupting sleep. In addition, the wavelength and intensity of light can negatively affect attention during the morning [ 68]. Given that the use of electronic devices may not be restricted completely, it is advisable not to use them at night in order to avoid the effects on sleep and health in general. In adults, a short nap has an impact on stress response. Cognitive disorders, such as the formation and storage of memory, including attention, executive functions, emotional reactivity, decision-making, and judgment, result in a reduction of their quality of life in general [ 69]. In this sense, a good night sleep is an essential factor for maintaining mental health on cognitive processes associated to learning and academic performance such as memory, attention, perception, and physical activity.

4.3. Nutrition

Academic performance may be susceptible to change or impact on various factors, such as those we have previously addressed like sleep and physical activity among others. However, it is important to know if the supply or nutrition can modify the student's academic performance or cognitive functioning, with the aim of generating strategies that support mental health in school-age children and adolescents. During childhood and adolescence, eating behaviors are very important. Given that in this stage, brain uses the most glucose or energy to the processes of attention, memory, and learning [ 70].

In addition to the breakfast hours, various analyses have noted the relationship between the types of food and academic performance. For example, fast food or "junk food" which contains the greatest number of calories and few nutrients. It was noted that low consumption of this type of food is associated with a better academic performance in children of preschool age, particularly with less consumption of sugary drinks [ 71]. As was expected, the intake of vegetables and fruit improves academic performance, although more studies are needed in this regard in different population [ 72].

A group of researchers recently analyzed the dietary effect of breakfast on scholar achievement in children from 8 to 15 years of age. The research consisted of a variety of diets such as fruit, vegetable, and sweetened drinks. The goal of the research was to analyze the relationship between the consumption of these diets and the grades of the students. The results showed that diet is associated with higher academic grades in children who consumed vegetables and fruits compared with those children who consumed sweetened drinks, who showed the lowest scores, mainly in grammar, reading, and writing [ 73].

The consumption of proteins and other nutrients from a diet of fish showed that there also exists a significant association related to academic performance and vocabulary scores in a study that observed 700 students between 12 and 18 years of age in the Netherlands. Nevertheless, more studies are necessary with respect to age, sex, and academic trajectory, as well as with different populations [ 74].

On the other hand, a recent study of a meta-analysis of 226 patients in a random study demonstrated that resveratrol, a natural phenolic compound contained in a normal diet, has been attributed to have a wide spectrum of biological properties, such as anti-carcinogen, anti-inflammatory, and antioxidant, in addition to a therapeutic effect on cognitive disorders. Resveratrol does not have an effect on memory or cognitive skills, including linguistic ability or retention of information [ 75].

However, the direct consumption of vitamins and other nutrients, such as iron, omega 3, among others, also shows a solid relationship between academic performance and intake [ 76]. The majority of studies suggest that there is an important association between the selective consumption of foods with the cognitive and academic performance. It is, therefore, necessary to research this further using animals in pre-clinical studies to provide sufficient evidence of the effect of diet, nutrients, and the quantity of food on the cognitive capacity and academic achievement.

5. Conclusion

This chapter has looked at studies in executive function and stress through the eyes of neurophysiology. Self-control of stress can promote a reduction in the action of the amygdala, and the subject can resolve the stressful situation. However, if we do not have control, it will cause alteration in the prefrontal cortex affecting the mental and physical health of the subject.

In relation to academic stressors, the lack of control strategies can promote increasing blood cortisol levels, which affect the psychomotor integrity of the individual. One of the factors that can affect executive functions is stress. The relationship between specific stressors and the deficit in executive functions in academic performance includes factors such as bullying and addictions. This knowledge leads to creating information strategies to alert teachers and parents about the consequences of these factors on cognition.

This chapter has also described a number of interventions designed to increase the level of executive function. Physical activity, good sleep, and nutrition at different stages of life are important factors for the maintenance of the body health. These are essential factors for maintaining mental health on cognitive processes associated with learning and academic performance such as memory, attention, and perception. The authors contend that using any of these different techniques may prove successful in alleviating the chronic or acute stress that permeates the school setting and is predictive of executive function deficits.

Acknowledgments

This chapter was partially supported by Catedras CONACYT project #1840 (National Council for Science and Technology) to ITCLL and DHB. Special thanks to the Nancy Gabriela Vázquez Ixtepan and Erick Hernández Baltazar for the art design, as well as to Miguel Angel Vallejo Vizcarra for the edition of this manuscript in English.

Tamara Cibrian-Llanderal, Montserrat Melgarejo-Gutierrez and Daniel Hernandez-Baltazar (September 19th 2018). Stress and Cognition: Psychological Basis and Support Resources, Health and Academic Achievement, Blandina Bernal-Morales, IntechOpen, DOI: 10.5772/intechopen.72566. Available from:

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Stress and Cognition: Psychological Basis and Support Resources | IntechOpen

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Executive functions are processes that help in tasks such as reasoning, planning, troubleshooting, and management of the individual's own life. A consequence of the specific connections of stress is that executive functions tend to be interrupted when the stimulation load is so big that the individual becomes stressed.

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Editorial: The Impact of Stress on Cognition and Motivation

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Editorial: The Impact of Stress on Cognition and Motivation

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"Even mild stressful events during this critical period can lead to long-lasting structural and neurochemical alterations and anxious- and depressive-like behaviors in the offspring."

Source: Editorial
Author: Pedro Morgado and João J. Cerqueira
Value: defines stress, outlines how various types of stress can impact cognition, describes specific hormone reactions to stress, describes pregnancy and stress

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Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS-3Bs PT Government Associate Laboratory, Guimarães, Portugal

Stress is usually defined as an actual or anticipated threat or disruption of organism homeostasis, which usually leads to an acute stress response allowing for adaptation to the new condition. Conversely, chronic stress usually leads to maladaptive responses in various organs and systems, activating pathophysiological mechanisms such as psychiatric disturbances, neurologic disorders, cardiovascular diseases and metabolic dysregulation ( Sousa, 2016). The impact of chronic stress in cognition and motivation has been extensively described in the literature. In this Research Topic of Frontiers in Behavioral Neuroscience, a host of new empirical findings on the impact of stress on cognition and motivation was presented in a translational perspective from rodents to humans.

The detrimental impact of stress on behavior can be established early in development, including from exposure before birth. Usually described as programming effects, these are well described after strongly stressful experiences during pregnancy. In one of the papers of this series, Soares-Cunha and co-workers extend our understanding of programming effects by showing that even mild stressful events during this critical period can lead to long-lasting structural and neurochemical alterations and anxious- and depressive-like behaviors in the offspring ( Soares-Cunha et al.).

Social stress is also known to induce depressive-like behaviors. Using tests based on association learning, Kúkel'ová et al. show that chronic social stress (CSS) can lead to reductions in reward salience and effort valuation in mice, decision-making deficits that can also be observed in patients depression and schizophrenia ( Kúkel'ová et al.), adding to the external validity of the model. Moreover, in another paper of the series, by Yang and collaborators, CSS induced spatial-working and contextual-fear memory deficits were related with decreased levels of N-methyl-D-aspartate receptor subunit 2B (NR2B), impaired long term potentiation (LTP) and NMDA receptor-mediated excitatory postsynaptic currents in the hippocampus ( Yang et al.). Importantly, both memory impairments and electrophysiological alterations were attenuated by antidepressant treatment with the NMDA-antagonist ketamine ( Yang et al.), adding further evidence to support a role for glutamate excitotoxicity in such stress-related deficits.

Although post-traumatic stress disorder (PTSD) is a widely recognized and often devastating consequence of exposure to intense stress, the biochemical mechanisms underlying the creation of the fear memory remain poorly understood. In a very interesting paper in this regard, Han and co-workers show that the behavioral consequences of exposure to a stress protocol designed to mimic a PTSD like-condition [single prolonged stress (SPS) protocol and immobilization-stress (IM)] are associated with decreased LTP as well as decreased stathmin and increased Rin1 expression in the hippocampus and the amygdala ( Han et al.). Of note, both regions are implicated in the regulation of fear memory, further stressing the significance of these findings.

The serotoninergic system has been involved in both anxiety state and trait, particularly through the activity of 5-HT2A receptors. To assess how anxiety trait can modulate the role of 5-HT2A in stress-induced anxiety, León and collaborators treated animals with high and low freezing responses to contextual cues previously associated with footshock with ketanserin, a preferential 5-HT2A receptor blocker. Their finding of an opposite effect of the drug on the two lines highlights and adds insight into the relevance of genetic variability in the establishment of stress responses ( León et al.).

Like serotonin, glial-derived neurotrophic factor (GDNF) has been implicated in the regulation of stress responses. Specifically, it was previously recognized that up-regulation of GDNF expression is associated with increased stress resilience. In a paper in the present Research Topic, Buhusi and co-authors extend this findings by showing that the opposite is also true: GDNF-deficient mice are more vulnerable to stress, failing to express latent inhibition (LI) which results in slower learning of new conditioning associations ( Buhusi et al.). Moreover, this LI impairment was associated with a decreased neuronal activation in the nucleus accumbens shell and increased activation in the nucleus accumbens core.

Decision-making processes are among the cognitive-related dimensions widely affected by stress. Work from ours and other groups has shown that chronic stress promotes a switch from a flexible and contextualized goal directed system of responses to a more rigid habit based system ( Dias-Ferreira et al., 2009). In line with this, a paper by Maran and colleagues in the present series shows that high arousal states disturb spatial and sequence learning, discrimination of spatial positions and learning of associative sequences, which could all reflect a reduced involvement of the flexible cognitive systems responsible for the sensitivity for contextual details ( Maran et al.).

We have previously shown that risk-based decision making is also impacted by chronic stress exposure ( Morgado et al., 2015). In the present Research Topic, Simonovic and colleagues translate our findings to humans, showing that stress exposure impairs performance in the Iowa Gambling Task (IGT), delaying the avoidance of the disadvantageous decks ( Simonovic et al.). In the same vein, Starcke and colleagues show that the exposure to unsolvable anagrams also induces more disadvantageous decisions on the IGT ( Starcke et al.), an effect particularly observed in male participants.

Given the vast consequences of stress exposure and its ubiquitous presence in our everyday lives, research on attenuating measures is of high clinical and even societal relevance. In a very interesting paper of this series, DiMenichi and co-authors show that writing about past failures before experiencing a stressor attenuated subsequent stress responses and reduced their physiological and behavioral effects ( DiMenichi et al.), a finding that can be easily transposed to practice.

Altogether, the findings put forward in this research topic contribute to a better understanding of how stress impacts on cognition and motivation, providing a broad range of insights from the molecular and cellular processes that underlie behavioral alterations to new interventions that can ameliorate stress-induced impairments.

Author Contributions

PM and JJC wrote this article and approved it for publication.

Funding

This work was supported by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and the BIAL foundation, Porto, Portugal (grant number PT/FB/BL-2016-206).

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

Dias-Ferreira, E., Sousa, J. C., Melo, I., Morgado, P., Mesquita, A. R., Cerqueira, J. J., et al. (2009). Chronic stress causes frontostriatal reorganization and affects decision-making. Science 325, 621-625. doi: 10.1126/science.1171203

PubMed Abstract | CrossRef Full Text | Google Scholar

Morgado, P., Marques, F., Ribeiro, B., Leite-Almeida, H., Pego, J. M., Rodrigues, A. J., et al. (2015). Stress induced risk-aversion is reverted by D2/D3 agonist in the rat. Eur. Neuropsychopharmacol. 25, 1744-1752. doi: 10.1016/j.euroneuro.2015.07.003

PubMed Abstract | CrossRef Full Text | Google Scholar

# data[].attributes.attachment_link.title
Editorial: The Impact of Stress on Cognition and Motivation

# data[].attributes.attachment_link.description
Stress is usually defined as an actual or anticipated threat or disruption of organism homeostasis, which usually leads to an acute stress response allowing for adaptation to the new condition. Conversely, chronic stress usually leads to maladaptive responses in various organs and systems, activating pathophysiological mechanisms such as psychiatric disturbances, neurologic disorders, cardiovascular diseases and metabolic dysregulation (Sousa, 2016).

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The Effects of Stress on Cognitive Aging, Physiology and Emotion (ESCAPE) Project

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The Effects of Stress on Cognitive Aging, Physiology and Emotion (ESCAPE) Project

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"A key objective of the ESCAPE (Effects of Stress on Cognitive Aging, Physiology, and Emotion) project is to evaluate whether engaging in stress-related unconstructive repetitive thought (URT) is a pathway through which stressful experiences negatively affect cognitive health over the short- and long-term."

Source: Study
Author: Stacey B. Scott et al.
Value: describes the impact of stress with relation to brain function, the function of the physical body, and its impact on general emotional function

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Project overview

The ESCAPE project is an ongoing longitudinal measurement burst study of a systematically recruited sample of racially and economically diverse 25-65 year olds residing in the Bronx, New York, U.S. Measurement burst designs consist of repeated sequences of closely spaced measurements [ 31- 33] that provide multiple time scales that allow for examination of processes unfolding within individuals over short time periods (e.g., minutes, hours, days) and how these processes change over longer time intervals (e.g., months, years; see [ 34]). The ESCAPE project consists of 4 longitudinal waves of data collection focused on cognition, stress, URT, and physiological variables. During each of these waves, participants complete a 14 day measurement burst. Each measurement burst consists of brief surveys and cognitive assessments administered on study-provided smartphones that participants complete up to 5 times per day as they go about their daily lives. This design will produce intensive data on each participant (i.e., 4 waves with 14 days of 5 momentary observations per day resulting in up to 280 momentary observations) across a 3 year period. With these data, we will be able to disentangle the time-ordering of the relationships outlined in the model in Fig. . Related to our short-term predictions, we will use the measurement burst data to examine the extent to which stressor occurrence, followed by engagement in URT, results in lower cognitive performance later in the day. Related to our long-term predictions, we will use the wave-to-wave longitudinal data to test whether the tendency to engage in URT predicts elevations in systemic inflammation and steeper decline in cognitive performance across three years.

Study site & participants

The Albert Einstein College of Medicine of Yeshiva University ethical review board approved the ESCAPE study protocol. Eligible participants are 25-65 years of age, ambulatory, fluent in English, free of visual impairment that would interfere with operating the study smartphone, and residing in Bronx County, New York. Exclusion criteria include inability to answer smartphone surveys throughout the day (e.g., due to work requirements or other commitments that would not allow participation in the study). The target sample size is 320 participants, which is based on power calculations required to identify small to medium sized effects for the primary study hypotheses.

The ESCAPE sample was selected to provide strong tests of the model in Fig. . First, the effects of stress on cognitive aging are theorized to accumulate across time and prior to old age; we therefore sampled young and middle-aged adults in order to capture this wear-and-tear as it occurs and affects cognitive functioning, prior to the full-blown development of cognitive impairment at older ages. Second, because both stress exposure and cognitive performance have been linked to socio-economic status, ESCAPE uses systematic probability sampling to recruit a racially and economically diverse sample of 25-65 year olds from Co-Op City, a Bronx, New York housing cooperative of approximately 60,000 residents.

Procedure

The ESCAPE protocol involves 4 waves of data collection across a 3 year period. Each wave, participants complete paper-based dispositional surveys, a lab visit, an EMA phase with smartphone surveys and cognitive tasks and saliva assessments, and a wrap-up visit with blood draws and other health assessments. Payments were paid upon completion of each wave. Payments for participation were based upon compliance rates with the study protocol. Participants received a maximum of $160 each wave if all lab visits, blood draws, paper and pencil surveys are completed as well as 80 % compliance was met on completion of burst phase smartphone surveys and cognitive assessments. Below, we elaborate on recruitment and each phase of data collection.

Recruitment

A sampling frame was developed from New York City Registered Voter Lists (RVL) obtained from the Board of Elections. Based on their age, individuals on the RVL were categorized into 10-year age bins and assigned to sampling blocks consisting of 450 potential participants in each bin. Individuals in a sampling block were sent letters of introduction, explaining the project's goals and how the recipient was identified. Within two weeks of sending recruitment letters, a follow up telephone call was conducted to establish rapport, identify exclusions, and enroll participants in the study.

Baseline and follow-up surveys

Following the recruitment phone call, consenting participants were mailed a baseline survey to complete at home. This survey contained demographic questions as well as detailed questionnaires about the major concentrations of this study - stress, URT, physical and mental health, and psychosocial factors that may moderate other observed relationships (see Measures section below and Table for a full description). At follow-up waves, participants received similar survey packets in the mail and completed them prior to returning the packets at their lab visit.

Table 1

Stress

Chronic

Role and environmental stress, neighborhood security, discrimination

Wheaton Chronic Stress (WCS) Scale, Lifetime Discrimination Scale, Neighborhood Safety and Violence Scale [ 70- 72]

URT

Event-related

Recurring thoughts about major stressor

Impact of Events Scale-Revised [ 75]

Momentary

Experiencing recurring, unwanted, negative thoughts

Momentary Thought Questionnaire

episodic memory

AVLT, Paired-associates, Card Memory Task

processing speed

Letter, Number and Symbol matching

fluid and crystallized intelligence

Ravens Progressive Matrices; Vocabulary

Ambulatory

LPS-stimulated cytokines

Plasma cytokines: IL-1β, IL-6, IL-8, IL-10, TNF-α, GM-CSF

Stress-related hormones

Salivary cortisol sampled 4 times per day for the first 5 days of each burst

Plasma cortisol; Plasma DHEAS

Subjective

Physical functioning, medical history, medication use, anxiety, depression, mood over last month, life satisfaction

PROMIS Physical Function Short Form-A, PROMIS Emotional Distress - Anxiety - Short Form 7-A, PROMIS Depression Short From 8-A, Positive and Negative Affect Schedule, Satisfaction with Life Scale [ 64, 76, 77]

Risk & Protective Factors

Risk

Neuroticism, social isolation, childhood adversity, anger

International Personality Item Pool (IPIP) Neuroticism subscale, PROMIS Social Isolation - Short Form-6a, Childhood Adversity subscale from WCS, State-Trait Anger Expression Inventory [ 70, 78, 79]

Protective

Conscientiousness, social support, positive events, optimism, adult temperament, mindfulness

IPIP Conscientiousness subscale, PROMIS Emotional, Informational, and Instrumental Social Support - Short Forms-6a, Pleasant Events Schedule, Life Orientation Test, Adult Temperament Questionnaire, Five Facet Mindfulness Questionnaire [ 64, 78, 80- 83]

Lab visits

At the initial lab visit for each wave, participants received training in the use of custom-configured smart phones for the measurement burst protocol and complete lab-based cognitive tasks.

Training session

In the training session, participants learned how to operate the study smartphone, practiced the smartphone survey questions and cognitive tests (described in Measures section) with the research assistant, and asked questions about the smartphones and protocol. Participants also received training in the use of the saliva collection kits (described in Measures section). The research assistant explained the schedule of data collection and showed participants the Help Line number on the back of the phone which they could call if they encountered problems with the smartphone or questions about the data collection.

Lab-based cognitive assessments

Lab-based cognitive assessments occurred at each wave and consisted of face-to-face and computer-based tests of working memory, episodic memory, and processing speed (see Measures section and Table ).

EMA practice phase

In the first wave of the study, participants completed a 2-day EMA practice phase after their initial lab visit and training. This served as a period in which participants became familiar with the study protocol. During the EMA practice phase, data was collected through smartphones and salivary assessments, described below. Participants returned to the lab at the end of the EMA practice phase and their compliance with the study protocol was calculated. Those participants who completed 80 % or more of morning, beeped, and bedtime smartphone surveys were invited into the burst phase of the study. Participants who did not meet compliance criteria were thanked and provided payment commensurate with their participation.

Smartphone surveys

Each morning, participants completed a brief smartphone survey about their previous night's sleep and their expectations regarding how pleasant and stressful the day ahead will be. The smartphone produced an audible alert ("beep") 5 times during the day, signaling participants to complete a survey about their recent stressors, current activities and emotions, and recent thoughts. At the completion of each of these surveys, the smartphone launched three brief cognitive tasks for the participant to complete. Beeps were scheduled in order to sample the entire waking day, with quasi-random timing to ensure that participants do not anticipate the beeps. At the end of each day, participants completed a separate bedtime survey in which they reported on their physical symptoms. The smartphone data was stored on the phone and data were sent in an encrypted format to a secure server upon completion of each survey.

Saliva assessments

Saliva was self-collected four times daily during the first 5 days of this period. Upon waking each morning, participants placed a synthetic Salivette (Sarstedt Inc., Newton NC) into their mouth and were instructed to chew on it gently until saturated. They then placed the Salivette into a pre-labeled collection tube and stored it in their refrigerator or freezer until their return visit to the clinic. Saliva samples were collected again in an identical manner 15 min and 30 min post-waking, and at bedtime. The specific times of sample collection were recorded by the participant on a form that was returned to investigators at the end of the burst.

Burst phase

Participants who met compliance criteria in the EMA practice phase were invited to follow the same protocol (i.e., 1 morning, 5 beeped, 1 evening survey each day) for 14 consecutive days. For the first 5 days of the burst phase, participants completed saliva assessments as in the EMA practice phase (i.e., upon waking, 15 min post-waking, 30 min post-waking, bedtime). Research staff made follow-up calls after the first day of smartphone surveys and again at the end of week 1 to motivate compliance and address any questions that arise during the burst assessments.

Wrap-up visit

Participants returned to the lab for a brief wrap-up visit after the 14-day burst phase and to return the study smartphones and saliva samples. During this visit a qualified phlebotomist obtained 12-h fasting blood samples, which were brought to the Institute for Clinical and Translational Research (ICTR) at Albert Einstein College of Medicine. The ICTR distributed samples for immediate analysis to the appropriate laboratories; samples were processed and aliquots of whole blood, plasma, and serum were stored at −70 °C for future analysis. Physical assessments were also obtained at this visit.

Longitudinal assessment schedule

There are 3 waves of follow-up data collection scheduled for 9, 18, and 27 months post baseline. As the study is currently in progress and has rolling recruitment, participants are currently in different waves. To limit participant burden, participants do not complete the EMA practice phase in follow-up waves. The first two lab visits were condensed into a single visit in which participants completed a brief refresher training on smartphone use and saliva collection, and they completed lab-based cognitive assessments. Prior to this visit, they completed a survey packet that included questionnaires to assess physical health, mental health, stress, personality, and psychosocial factors (e.g., social support). Participants next completed the burst phase, and then the wrap-up visit.

Measures

The measures and timing of participants' assessments are summarized in Table . Below, we describe the central domains assessed.

Demographic

In addition to conventional demographic variables describing stable characteristics of individuals (e.g., age, race, ethnicity, gender) assessed at baseline, we conducted follow-up assessments of aspects of individuals' life context that may vary over time (e.g., income, work, marital status) that may vary over time and affect exposure and response to stressors.

Stress

The term "stress" describes a multicomponent process that, as measured in ESCAPE, has four major components that are aligned with different time-scales. Specific measures used to assess each component are shown in Table . Chronic stress describes sources of stress (e.g., caregiving, dangerous neighborhood; [ 35, 36]), many of which do not have clear onset or endings. Major life events are infrequent, dramatic stressors, and include events such as divorce, widowhood. Subjective stress describes general appraisal of the state of feeling distressed or overwhelmed over the last month. Daily events are possibly more frequent and/or recurrent stressors that are less dramatic and include events such as arguments and deadlines. Table describes the specific instruments employed in ESCAPE to measure these components of stress (i.e., chronic stress, major life events, subjective stress, and daily events).

Unconstructive Repetitive Thoughts (URT)

We also assessed several different ways in which URT may play a role in individuals' responses to major life events, chronic stressors, and daily hassles. Table describes the specific measures used to assess both dispositional and state (i.e., momentary) URT. First, dispositional URT describes tendencies for some individuals to engage in recurrent negative thoughts more than others, both in general [ 37, 38] as well as in response to specific sources of major life stress [ 39]. We expect that dispositional measures (i.e., WBSI, RRQ, IES-R) will operate through influencing the frequency and intensity of momentary experiences of URT, both in response to a stressor as well as in the absence of external triggers. S tate URT was assessed using 4 items developed for this study. These items ask individuals to use a continuous visual analogue scale (a slider) to rate the thoughts they had experienced in the 5 min prior to completing the smartphone survey in terms of their overall valence (unpleasant-pleasant), negative self-focus ("Were you thinking about personal problems or worries?"), and controllability ("Were you experiencing a train of thought that you couldn't get out of your head?" and "Were you preoccupied with thoughts of something about to happen or that might happen in the future?").

Cognition

We used two complementary approaches to assessing cognitive function. First, lab-based cognition was assessed during visits to the research clinic by a trained technician in a controlled testing environment. Second, ambulatory cognition was assessed repeatedly via smartphones in naturalistic settings as people go about their daily activities. We expect that ambulatory assessments will provide a more ecologically valid characterization of individuals' cognitive functioning that will complement and extend traditional lab-based assessments.

Lab-based cognitive assessments included fluid intelligence and crystallized intelligence, assessed by the Raven's Progressive Matrices [ 40], and the WRAT/Vocabulary [ 41], in addition to working memory, episodic memory, and processing speed. Working memory (WM) reflects a person's ability to manipulate and maintain information in an active form. Three standardized tasks were used to measure WM in the lab: counting span, operation span [ 42, 43], and the backwards letter-span task [ 44]. Episodic memory was measured using the Auditory Verbal Learning Test (AVLT) [ 45] and a word-number paired associates learning task [ 46]. The "Card-memory Task" (CMT) required participants to learn the location of 6 playing cards that appear on a computer monitor, and recall those locations after completing a visual distractor task. Participants completed two choice reaction time tasks as measures of processing speed. In two separate tasks, participants completed two strings of characters (letters or numbers) as quickly as possible. Strings were 3, 6, or 9 characters in length to provide a variety of difficulty levels for analysis. The Symbol-symbol comparison task required participants to decide as quickly as possible whether a target pair of non-verbalizable symbols matches any of a set of five comparison pairs. Stimuli were randomly generated for each of cognitive tasks to avoid stimulus specific learning effects across repeated measures.

Ambulatory cognition was assessed on the smartphone by three tasks presented after each beeped survey in the following fixed order: processing speed, spatial working memory, and verbal working memory. Screen shots are provided in Fig. . The smartphone processing speed tasks required participants to compare three symbol pairs at the top of the screen and with two symbol pairs at the bottom of the screen and decide as quickly as possible which of the two pairs presented at the bottom of the screen is among the pairs at the top of the screen (see Fig. ). The location memory task assessed s patial working memory and required participants to memorize the location of three red dots that appear on a 5 x 5 grid for 3 s (see Fig. ). After a visual distractor exercise of 8-s (see Fig. ), participants then recalled the locations of the 3 dots (see Fig. ). The v erbal working memory was adapted from the columnized n-back paradigm [ 47], and included a 0-back and 2-back condition. Participants saw a series of 3 standard playing cards (see Fig. ) slide from one box on the right of the screen to the second box on left of the screen (see Fig. ). They completed a 0-back and 2-back variation of the standard n-back task. In the 0-back, cards face up and participants were asked to determine whether the cards in the two boxes match. In the 2-back variation, the previous two cards face down (see Fig. ). Each assessment consisted of 16 symbol comparison trials, 2 dot-memory trials, and 12 2-back trials.

Physiological measures of stress and endocrine function

Our primary marker of endocrine function in ESCAPE is cortisol, which is the primary glucocorticoid (GC) in humans and an important stress hormone. The majority of our cortisol variables were derived from salivary assessments, including cortisol awakening response (CAR) and area under the curve (AUC). The CAR is of particular importance to the ESCAPE study because it can be used to identify a blunted CAR, which is a signature of chronic stress [ 48]. Blood samples were also used to determine plasma cortisol and dehydroepiandrosterone sulfate (DHEAS). DHEAS is an adrenal hormone that both suppresses cortisol production and antagonizes its immunosuppressive (anti-inflammatory) effects [ 49, 50]. As a low DHEAS/cortisol ratio has been linked with a range of clinical outcomes, including cognitive impairment and senile dementia [ 51], the ESCAPE study will evaluate the effects of stress on this ratio and its role in explaining the impact of stress on cognition. Further, DHEAS declines with age and reductions in the DHEAS/cortisol ratio may explain why the deleterious consequences of HPA axis activation increase with age [ 52- 56].

Assay details

At the end of each burst, cortisol levels were determined employing a competitive solid phase time-resolved fluorescence immunoassay with fluorometric end point detection (DELFIA). The intra-assay coefficient of variation (CV) is 4.0-6.7 % and the inter-assay CV is 7.1-9.0 %. Plasma, obtained at the end of each burst, is assayed to determine cortisol and DHEAS levels by enzyme-linked immunosorbent assay (ELISA) (IBL International Corp., Toronto ON). The minimum detection limit for cortisol is 2.46 ng/ml, and its inter- and intra-assay CVs are 2-5 %. The minimum detection limit for DHEAS is 4 pg/ml and its inter- and intra-assay CVs are 4-7 %. All of the above assays were performed in duplicate.

Physiological measures of inflammation

The majority of studies linking cognition and inflammation have not examined more than one or two inflammatory markers at a time. This study takes a multivariable approach, and simultaneously assesses ten pro- and anti-inflammatory biomarkers: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and granulocyte macrophage colony-stimulating factor (GM-CSF; assay details described below). We also determined circulating plasma levels of C-reactive protein (CRP), which has widespread use clinically as a well-validated and sensitive marker of systemic inflammation [ 57]. Stimulated ex vivo inflammatory cytokine responses were also measured. For this purpose, a subset of whole blood (1 mL) was incubated with 1 μg/mL lipopolysaccharide (LPS). LPS is an antigen that stimulates immune cells and can thus be used to quantify the inflammatory response that cells in whole blood generate to an immune challenge. This provides a dynamic measure of inflammatory change that is unique from that of basal inflammation, and which may differentially relate to stress and cognition. Because not all cytokine levels rise significantly in response to ex vivo LPS stimulation, a subset of cytokines were assessed in LPS-stimulated blood: IL-1β, IL-6, IL-8, IL-10, TNF-α, and GM-CSF.

Importantly, the various inflammatory biomarkers determined in the ESCAPE study serve different functions and may therefore exhibit different response patterns to stress. This study thus allows for an inflammatory profile to be determined for each individual at a given time point, which is more reliable, valid, and informative than the rise or fall of a single biomarker. We expect the pattern in which these profiles change across years will be more predictive of cognitive aging than changes in any single measure of inflammation.

Assay details

Basal and LPS-stimulated cytokine levels were determined using multiplex magnetic bead arrays (Life Technologies, Grand Island NY). Multiplex bead arrays have advantages over standard ELISAs, including simultaneous measurement of interrelated cytokines, high sensitivity, and reductions in inter-plate variability, cost of analysis, and the amount of time and sample needed. The minimum detection limit for these assays is less than 0.5 pg/ml for each analyte and inter-assay CVs are 4.4 %-8.6 %. CRP is determined from blood plasma using ELISA (Cayman Chemical, Ann Arbor MI); the minimum detection limit is .047 ng/ml (.000047 mg/L) and intra-assay CV is 2 %-7 %. All assays were performed in duplicate.

Physical and mental health

ESCAPE includes both objective and subjective assessments of health. In order to examine longitudinal changes in indicators of overall physical health, participants completed blood draws and physical assessments (e.g., BP, waist-to-hip ratio). Participants also provided subjective reports of their physical functioning, medical history, and medication use.

Overall mental health was assessed via self-reports of anxiety, depression, and anger using standardized measures from the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS). In the momentary smartphone surveys, participants reported on their current emotional states (anger, anxiety, depression), which will allow us to track predictors of dynamic shifts in affective states as well as obtain more ecologically valid assessments of mental health than single-shot questionnaires can provide.

Risk and protective factors

Individual difference characteristics (i.e., personality, psychosocial resources, life orientation) as well in as lifetime experiences (i.e., childhood adversity, positive life events) may moderate the relationships among stress, URT, and cognitive function. ESCAPE includes measures of both risk and protective factors, as described in Table .

Analytic approach

As described above, the primary objectives of the ESCAPE study are to examine whether URT operates as an important psychological pathway by which stressors exert their adverse effects on cognitive health, and to examine whether stress-related alterations in HPA-axis function and inflammation help explain those connections at a physiological level. These objectives will be accomplished by examining both the short-term effects and long-term effects of stress on cognitive function.

Short-term tests

With regard to shorter term effects, we will evaluate the hypothesis that URT contributes to short-term (daily) stress effects on cognition via two sets of analyses. First, we will fit an autoregressive multilevel mixed model (MLM; [ 58]) to burst data to establish a lagged association between daily stress and ambulatory cognitive function, controlling for current stress, fatigue, mood, and other momentary covariates. Multilevel modeling is required because the burst data consists of repeated observations nested within persons. After establishing the lagged effect of daily stressors on working memory, we will then follow multi-level mediation procedures described in Bauer and colleagues [ 59] to test whether daily URT significantly mediates this relationship. Second, we will use structural MLM [ 60] to examine whether components of daily stress (e.g., exposure and reactivity) predict higher levels of systemic inflammation and altered inflammatory responses, and whether inflammation explains the association between daily stress and ambulatory memory function.

Long-term tests

To elucidate longer-term effects, we will use structural equation modeling (SEM; [ 61]). In these models, we will test the hypotheses that URT (at the psychological level), and evidence of HPA-axis dysregulation and inflammation (at the physiological level), mediate long-term effects of chronic stress on cognitive function. We will use baseline data to first determine whether individual differences in the tendency to engage in URT mediates the effects of chronic stress on current levels of ambulatory (assessed by smartphone) and lab-based measures of cognitive function. These analyses will be followed by SEM analyses that examine whether 1) those who have experienced greater chronic stress will have lower (blunted) values for cortisol area under the curve (AUC) and CAR, and elevated basal and inflammatory responses, 2) a blunted AUC and CAR predict greater inflammation, and 3) inflammation account for associations between chronic stress and cognition measures. Next, we will conduct longitudinal analyses using MLM to test the prediction that URT mediates the effects of chronic stress on the rates of cognitive change across measurement bursts. In this analysis, chronic stress will be treated as a time-varying predictor of intraindividual cognitive change across the four year follow-up, and URT will be examined as a time-varying mediator. Similarly, in analyses adding in HPA-axis and inflammatory markers we expect that AUC, CAR, and inflammatory changes will mediate the effects of chronic stress on intraindividual cognitive change. Sliwinski and colleagues provide a detailed description and example of this analytic approach in a study that examined long-term intraindividual changes in daily stress and negative affect [ 62].

Missing data/attrition

Some participants will not complete all planned measurements. Our use of general linear mixed models will insure unbiased results as long as missing data depend only upon observed variable (i.e., missing at random [MAR]). We will conduct sensitivity analysis using pattern mixture methods (e.g., [ 63]) to assess possible effects of informative attrition on study conclusions. Item-level missing data will be imputed using standardized guidelines specific to each questionnaire when available (e.g., PROMIS measures). In other cases, if the amount of missing data for a questionnaire is small (e.g. <5 %), we will consider calculating prorated scale scores to minimize casewise deletion.

Sample size calculations

Our power analysis considered sample size requirements for conducting both between-person and within-person statistical tests with an alpha level set to .05. For testing between-person effects we determine the necessary sample for detecting a small effect of stress on cognition (partial r = .16) using a general linear model. We selected this effect size based on our previous work [ 14]. This yielded a necessary sample size of approximately N = 310. Determining power for within-person tests conducted by multilevel analysis is complex, as values for many different parameters (e.g., intercept, slope, residual variance, covariances) must be specified. For simplicity, we assumed dependent variables were standardized (mean = 0, variance = 0) and the intraclass correlation ranged between .4 and .6 for the smartphone cognitive measures. Using these assumptions we conducted Monte Carlo (using SAS IML and MPLUS) simulations to determine the minimum detectable within-person effect assuming an initial sample of 300 and attrition rate of 20 % at burst 2, and 10 % at each burst thereafter. Results from our simulations yielded power of at least .80 for detecting small within-person effects on cognition that could account for at least 3 % of the variance.

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The Effects of Stress on Cognitive Aging, Physiology and Emotion (ESCAPE) Project

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The ESCAPE project is an ongoing longitudinal measurement burst study of a systematically recruited sample of racially and economically diverse 25-65 year olds residing in the Bronx, New York, U.S.