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.