The kindling phenomenon is a form of sensitization where, with repetition, epileptiform discharges become progressively longer and behavioral seizures eventually appear and then become more severe. The classic or exogenous kindling technique involves the repeated application of a convulsant stimulus. This technique also lowers seizure thresholds, the minimum intensity of a stimulus required to evoke an electrographic seizure, a process known as epileptogenesis. Endogenous kindling typically occurs following a brain-damaging event which lowers seizure thresholds to the point where self-generated epileptiform discharges recur, lengthen, propagate, and drive progressively more severe behavioral seizures. While exogenous kindling results in alterations in neuronal molecular, cellular/synaptic, and network function that give rise to altered behavior, there is a paucity of evidence for loss of neurons. In contrast, brain-damaging events, with neuronal loss, typically give rise to endogenous kindling. Kindling is a pan-species phenomenon and all mammals that have been examined, including humans, manifest exogenous kindling when seizure-genic (forebrain) structures have been targeted. Since humans display both exogenous and endogenous kindling phenomena this serves as a sober warning to clinicians to prevent seizures. Kindling serves as a robust and reliable model for epileptogenesis, focal as well as secondarily generalized seizures, and certain epileptic disorders.
G. Campbell Teskey
Determining the mechanisms that underlie neurocognitive aging, such as compensation or dedifferentiation, and facilitating the development of effective strategies for cognitive improvement is essential due to the steadily rising aging population. One approach to study the characteristics of healthy aging comprises the assessment of functional connectivity, delineating markers of age-related neurocognitive plasticity. Functional connectivity paradigms characterize complex one-to-many (or many-to-many) structure–function relations, as higher-level cognitive processes are mediated by the interaction among a number of functionally related neural areas rather than localized to discrete brain regions. Task-related or resting-state interregional correlations of brain activity have been used as reliable indices of functional connectivity, delineating age-related alterations in a number of large-scale brain networks, which subserve attention, working memory, episodic retrieval, and task-switching. Together with behavioral and regional activation studies, connectivity studies and modeling approaches have contributed to our understanding of the mechanisms of age-related reorganization of distributed functional networks; specifically, reduced neural specificity (dedifferentiation) and associated impairment in inhibitory control and compensatory neural recruitment.
Thomas M. Hess, Erica L. O'Brien, and Claire M. Growney
Blood pressure is a frequently used measure in studies of adult development and aging, serving as a biomarker for health, physiological reactivity, and task engagement. Importantly, it has helped elucidate the influence of cardiovascular health on behavioral aspects of the aging process, with research demonstrating the negative effect of chronic high blood pressure on various aspects of cognitive functioning in later life. An important implication of such research is that much of what is considered part and parcel of getting older may actually be reflective of changes in health as opposed to normative aging processes. Research has also demonstrated that situational spikes in blood pressure to emotional stressors (i.e., reactivity) also have implications for health in later life. Although research is still somewhat limited, individual differences in personal traits and living circumstances have been found to moderate the strength of reactive responses, providing promise for the identification of factors that might ameliorate the effects of age-related changes in physiology that lead to normative increases in reactivity. Finally, blood pressure has also been successfully used to assess engagement levels. In this context, recent work on aging has focused on the utility of blood pressure as a reliable indicator of both (a) the costs associated with cognitive engagement and (b) the extent to which variation in these costs might predict both between-individual and age-related normative variation in participation in cognitively demanding—but potentially beneficial—activities. This chapter elaborates on these three approaches and summarizes major research findings along with methodological and interpretational issues.
Stephanie J. Wilson, Alex Woody, and Janice K. Kiecolt-Glaser
Inflammatory markers provide invaluable tools for studying health and disease across the lifespan. Inflammation is central to the immune system’s response to infection and wounding; it also can increase in response to psychosocial stress. In addition, depression and physical symptoms such as pain and poor sleep can promote inflammation and, because these factors fuel each other, all contribute synergistically to rising inflammation. With increasing age, persistent exposure to pathogens and stress can induce a chronic proinflammatory state, a process known as inflamm-aging. Inflammation’s relevance spans the life course, from childhood to adulthood to death. Infection-related inflammation and stress in childhood, and even maternal stress during pregnancy, may presage heightened inflammation and poor health in adulthood. In turn, chronically heightened inflammation in adulthood can foreshadow frailty, functional decline, and the onset of inflammatory diseases in older age. The most commonly measured inflammatory markers include C-reactive protein (CRP) and proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). These biomarkers are typically measured in serum or plasma through blood draw, which capture current circulating levels of inflammation. Dried blood spots offer a newer, sometimes less expensive collection method but can capture only a limited subset of markers. Due to its notable confounds, salivary sampling cannot be recommended. Inflammatory markers can be added to a wide range of lifespan developmental designs. Incorporating even a single inflammatory assessment to an existing longitudinal study can allow researchers to examine how developmental profiles and inflammatory status are linked, but repeated assessments must be used to draw conclusions about the associations’ temporal order and developmental changes. Although the various inflammatory indices can fluctuate from day to day, ecological momentary assessment and longitudinal burst studies have not yet incorporated daily inflammation measurement; this represents a promising avenue for future research. In conclusion, mounting evidence suggests that inflammation affects health and disease across the lifespan and can help to capture how stress “gets under the skin.” Incorporating inflammatory biomarkers into developmental studies stands to enhance our understanding of both inflammation and lifespan development.