Stress is encountered by every individual on a daily basis. Such encounters can be of a negative (distress) or a positive (eustress) nature. Excessive and chronic distress exposure is associated with numerous health problems affecting both physiological and psychological components of a person’s well-being. One mediating aspect of these occurrences is the responses of the neuroendocrine system with the body. Physical activity (i.e., exercise) produces large and dramatic changes in the neuroendocrine system as it serves as a “stressor” to the system. To this end, though, chronic engagement in physical activity leads to exercise training-induced adaptations within the neuroendocrine system that potentiate an individual’s ability to deal with distressful experiences and exposures. Therefore, becoming more physically fit and exercise trained is one potential adjunctive therapy available for clinicians to recommend in the treatment of health problems associated with chronic exposure to distress.
Anthony C. Hackney and Eser Ağgön
Robert J. McDonald and Ellen G. Fraser
One view of the organization of learning and memory functions in the mammalian brain is that there are multiple learning and memory networks that acquire and store different kinds of information. Each neural network is thought to have a central structure. The hippocampus, amygdala, perirhinal cortex, and dorsal striatum are thought to be central structures for different learning and memory networks important for spatial/relational, emotional, visual objects, and instrumental memory respectively. These central structures are part of a complex network including cortical and subcortical brain regions containing areas important for sensory, motivational, modulatory, and output functions. These networks are thought to encode and store information obtained during experiences via a general plasticity mechanism in which the relationship between synapses in these regions are changed. This view suggests that that memory has a physical manifestation in the brain, which allows for synapses to communicate more effectively as a result of activation. One form of synaptic plasticity called long-term potentiation (LTP) is considered a fundamental form of changes in synaptic efficacy mediating learning and long-term memory functions. One of the biochemical mechanisms for initiating LTP is triggered when a type of glutamate receptor, N-methyl-D-aspartate receptor (NMDAR), found in all of these memory networks is activated and various biochemical pathways that can produce long-term enhancements to the efficacy of that synapse are recruited. NMDAR-mediated LTP processes appear to be important for learning and memory processes in these different networks, but there are clear differences. None of the networks require NMDAR functions during expression of new learning. All the networks required NMDAR function during encoding of new information, except the network centered on perirhinal cortex. Finally, all of the networks required NMDAR-mediated plasticity processes for long-term consolidation of new information, except the one centered on the amygdala.
Patrick D. Gajewski and Michael Falkenstein
Healthy aging is associated with changes in sensory, motor, cognitive, and emotional functions. Such changes depend on various factors. In particular, physical activity not only improves physical and motor but also cognitive and emotional functions. Observational (i.e., associations) and cross-sectional studies generally show a positive effect of regular physical exercise on cognition in older adults. Most longitudinal randomized controlled intervention studies also show positive effects, but the results are inconsistent due to large heterogeneity of methodological setups. Positive changes accompanying physical activity mainly impact executive functions, memory functions, and processing speed. Several factors influence the impact of physical activity on cognition, mainly the type and format of the activity. Strength training and aerobic training yield comparable but also differential benefits, and all should be used in physical activities. Also, a combination of physical activity with cognitive activity appears to enhance its effect on cognition in older age. Hence, such combined training approaches are preferable to homogeneous trainings. Studies of brain physiology changes due to physical activity show general as well as specific effects on certain brain structures and functions, particularly in the frontal cortex and the hippocampus, which are those areas most affected by advanced age. Physical activity also appears to improve cognition in patients with mild cognitive dysfunction and dementia and often ameliorates the disease symptoms. This makes physical training an important intervention for those groups of older people. Apart from cognition, physical activity leads to improvement of emotional functions. Exercise can lead to improvement of psychological well-being in older adults. Most importantly, exercise appears to reduce symptoms of depression in seniors. In future intervention studies it should be clarified who profits most from physical activity. Further, the conditions that influence the cognitive and emotional benefits older people derive from physical activity should be investigated in more detail. Finally, measures of brain activity that can be easily applied should be included as far as possible.
The role of experience in brain organization and function can be studied by systematically manipulating developmental experiences. The most common protocols use extremes in experiential manipulation, such as environmental deprivation and/or enrichment. Studies of the effects of deprivation range from laboratory studies in which animals are raised in the absence of sensory or social experiences from infancy to children raised in orphanages with limited caregiver interaction. In both cases there are chronic perceptual, cognitive, and social dsyfunctions that are associated with chronic changes in neuronal structure and connectivity. Deprivation can be more subtle too, such as being raised in a low socioeconomic environment, which is often associated with poverty. Such experience is especially detrimental to language development, which in turn, limits educational opportunities. Unfortunately, the effects of some forms of socioemotional deprivation are often difficult, if not impossible, to ameliorate. In contrast, adding sensory or social experiences can enhance behavioral functions. For example, placing animals in environments that are cognitively, motorically, and/or socially more complex than standard laboratory housing is associated with neuronal changes that are correlated with superior functions. Enhanced sensory experiences can be relatively subtle, however. For example, tactile stimulation with a soft brush for 15 minutes, three times daily for just two weeks in infant rats leads to permanent improvement in a wide range of psychological functions, including motoric, mnemonic, and other cognitive functions. Both complex environments and sensory stimulation can also reverse the negative effects of many other experiences. Thus, tactile stimulation accelerates discharge from hospital for premature human infants and stimulates recovery from stroke in both infant and adult rats. In sum, brain and behavioral functions are exquisitely influenced by manipulation of sensory experiences, especially in development.
The process of brain development begins shortly after conception and in humans takes decades to complete. Indeed, it has been argued that brain development occurs over the lifespan. A complex genetic blueprint provides the intricate details of the process of brain construction. Additional operational instructions that control gene and protein expression are derived from experience, and these operational instructions allow an individual to meet and uniquely adapt to the environmental demands they face. The science of epigenetics provides an explanation of how an individual’s experience adds a layer of instruction to the existing DNA that ultimately controls the phenotypic expression of that individual and can contribute to gene and protein expression in their children, grandchildren, and ensuing generations. Experiences that contribute to alterations in gene expression include gonadal hormones, diet, toxic stress, microbiota, and positive nurturing relationships, to name but a few. There are seven phases of brain development and each phase is defined by timing and purpose. As the brain proceeds through these genetically predetermined steps, various experiences have the potential to alter its final form and behavioral output. Brain plasticity refers to the brain’s ability to change in response to environmental cues or demands. Sensitive periods in brain development are times during which a part of the brain is particularly malleable and dependent on the occurrence of specific experiences in order for the brain to tune its connections and optimize its function. These periods open at different time points for various brain regions and the closing of a sensitive period is dependent on the development of inhibitory circuitry. Some experiences have negative consequences for brain development, whereas other experiences promote positive outcomes. It is the accumulation of these experiences that shape the brain and determine the behavioral outcomes for an individual.
Michael J. Valenzuela
Cognitive reserve refers to the many ways that neural, cognitive, and psychosocial processes can adapt and change in response to brain aging, damage, or disease, with the overarching effect of preserving cognitive function. Cognitive reserve therefore helps to explain why cognitive abilities in late life vary as dramatically as they do, and why some individuals are brittle to degenerative pathology and others exceptionally resilient. Historically, the term has evolved and at times suffered from vague, circular, and even competing notions. Fortunately, a recent broad consensus process has developed working definitions that resolve many of these issues, and here the evidence is presented in the form of a suggested Framework: Contributors to cognitive reserve, which include environmental exposures that demand new learning and intellectual challenge, genetic factors that remain largely unknown, and putative G × E interactions; mechanisms of cognitive reserve that can be studied at the biological, cognitive, or psychosocial level, with a common theme of plasticity, flexibility, and compensability; and the clinical outcome of (enriched) cognitive reserve that can be summarized as a compression of cognitive morbidity, a relative protection from incident dementia but increased rate of progression and mortality after diagnosis. Cognitive reserve therefore has great potential to address the global challenge of aging societies, yet for this potential to be realized a renewed scientific, clinical, and societal focus will be required.